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Sample records for oxycodone controlled release

  1. Oxycodone controlled release in cancer pain management.

    PubMed

    Biancofiore, Giuseppe

    2006-09-01

    Oral opioids are the treatment of choice for chronic cancer pain. Morphine is the strong opioid of choice for the treatment of moderate to severe cancer pain according to guidelines from the World Health Organization (WHO). This recommendation by the WHO was derived from availability, familiarity to clinicians, established effectiveness, simplicity of administration, and relative inexpensive cost. It was not based on proven therapeutic superiority over other options. Patients who experience inadequate pain relief or intolerable side effects with one opioid may often be successfully treated with another agent or with the same agent administered by a different route. Opioid rotation, or switching to an alternative opioid, helps some patients achieve better pain control with fewer associated adverse effects. Oxycodone is a mu-opioid receptor specific ligand, with clear agonist properties. It is an active potent opioid, which is in part a kappa-receptor agonist. Like morphine and other pure agonists, there is no known ceiling to the analgesic effects of oxycodone. The active metabolites of oxycodone (eg, oxymorphone) could be important in oxycodone-mediated analgesia. The main pharmacokinetic difference between oxycodone and morphine is in oral bioavailability. The bioavailability of oxycodone is >60% and the bioavailability of morphine is 20%. Controlled-release oxycodone is absorbed in a bi-exponential fashion. There is a rapid phase with a mean half-life of 37 min, accounting for 38% of the dose, and a slow phase with a half-life of 6.2 h, which accounts for the residual 62%. Oxycodone elimination is impaired by renal failure because there are both an increased volume of distribution and reduced clearance. A lot of studies prove that the efficacy of controlled-release oxycodone in cancer-pain control is at least the same as morphine, immediate-release oxycodone and hydromorphone. Its toxicity profile seems better than that of morphine. There are actually several

  2. Analgesic efficacy of controlled-release oxycodone in postoperative pain.

    PubMed

    Sunshine, A; Olson, N Z; Colon, A; Rivera, J; Kaiko, R F; Fitzmartin, R D; Reder, R F; Goldenheim, P D

    1996-07-01

    The efficacy and safety of graded doses (10, 20, and 30 mg) of controlled-release (CR) oxycodone was compared with that of immediate-release (IR) oxycodone (15 mg), immediate-release oxycodone 10 mg in combination with acetaminophen 650 mg (APAP), and placebo in a single-dose, double-blind, randomized, parallel-group study. The participants, 182 inpatients experiencing moderate to severe pain after abdominal or gynecologic surgery, provided hourly ratings of pain intensity and relief for 12 hours after administration. All active treatments were significantly superior to placebo for many hourly measurements and for the sum of pain intensity differences (SPID) and total pain relief (TOTPAR). A dose response was found among the three levels of CR oxycodone for pain relief and peak pain intensity difference (PID), with the 20- and 30-mg doses being significantly better than the 10-mg dose. For all active treatments, peak PID and peak pain relief occurred approximately 2 to 4 hours after administration. The median time to onset of relief was 32 minutes for oxycodone plus APAP, 41 minutes for IR oxycodone, and 46 minutes for CR oxycodone 30 mg. Duration of pain relief showed that the 10-, 20-, and 30-mg doses of CR oxycodone had durations of action of 10 to 12 hours compared with IR oxycodone and oxycodone plus APAP (both approximately 7 hours). Typical adverse events, particularly somnolence, occurred in all active treatment groups. Treatment with CR oxycodone was safe and effective in this study, and its characteristics will be beneficial in the treatment of pain. PMID:8844441

  3. Controlled-release oxycodone and naloxone in the treatment of chronic low back pain: A placebo-controlled, randomized study

    PubMed Central

    Cloutier, C; Taliano, J; O’Mahony, W; Csanadi, M; Cohen, G; Sutton, I; Sinclair, D; Awde, M; Henein, S; Robinson, L; Eisenhoffer, J; Piraino, PS; Harsanyi, Z; Michalko, KJ

    2013-01-01

    BACKGROUND For Canadian regulatory purposes, an analgesic study was required to complement previously completed, pivotal studies on bowel effects and analgesia associated with controlled-release (CR) oxycodone/CR naloxone. OBJECTIVES: To compare the analgesic efficacy and safety of CR oxycodone/CR naloxone versus placebo in patients with chronic low back pain. METHODS: Patients requiring opioid therapy underwent a two- to seven-day opioid washout before being randomly assigned to receive either 10 mg/5 mg CR oxycodone/CR naloxone or placebo every 12 h, titrated weekly according to efficacy and tolerability to 20 mg/10 mg, 30 mg/15 mg or 40 mg/20 mg every 12 h. After four weeks, patients crossed over to the alternative treatment for an additional four weeks. Acetaminophen/codeine (300 mg/30 mg every 4 h to 6 h as needed) was provided as rescue medication. RESULTS: Of the 83 randomized patients, 54 (65%) comprised the per-protocol population. According to per-protocol analysis, CR oxycodone/CR naloxone resulted in significantly lower mean (± SD) pain scores measured on a visual analogue scale (48.6±23.1 mm versus 55.9±25.4 mm; P=0.0296) and five-point ordinal pain intensity scores (2.1±0.8 versus 2.4±0.9; P=0.0415) compared with placebo. After the double-blinded phase, patients and investigators both preferred CR oxycodone/CR naloxone over placebo. These outcomes continued in the 79% of patients who chose to continue receiving CR oxycodone/CR naloxone in a six-month, open-label evaluation. CONCLUSIONS: In patients complying with treatment as per protocol, CR oxycodone/CR naloxone was effective for the management of chronic low back pain of moderate or severe intensity. PMID:23662289

  4. Slow drug delivery decreased total body clearance and altered bioavailability of immediate- and controlled-release oxycodone formulations.

    PubMed

    Li, Yan; Sun, Duxin; Palmisano, Maria; Zhou, Simon

    2016-02-01

    Oxycodone is a commonly used analgesic with a large body of pharmacokinetic data from various immediate-release or controlled-release formulations, under different administration routes, and in diverse populations. Longer terminal half-lives from extravascular administration as compared to IV administration have been attributed to flip-flop pharmacokinetics with the rate constant of absorption slower than elimination. However, PK parameters from the extravascular studies showed faster absorption than elimination. Sustained release formulations guided by the flip-flop concept produced mixed outcomes in formulation development and clinical studies. This research aims to develop a mechanistic knowledge of oxycodone ADME, and provide a consistent interpretation of diverging results and insight to guide further extended release development and optimize the clinical use of oxycodone. PK data of oxycodone in human studies were collected from literature and digitized. The PK data were analyzed using a new PK model with Weibull function to describe time-varying drug releases/ oral absorption, and elimination dependent upon drug input to the portal vein. The new and traditional PK models were coded in NONMEM. Sensitivity analyses were conducted to address the relationship between rates of drug release/absorption and PK profiles plus terminal half-lives. Traditional PK model could not be applied consistently to describe drug absorption and elimination of oxycodone. Errors were forced on absorption, elimination, or both parameters when IV and PO profiles were fitted separately. The new mechanistic PK model with Weibull function on absorption and slower total body clearance caused by slower absorption adequately describes the complex interplay between oxycodone absorption and elimination in vivo. Terminal phase of oxycodone PK profile was shown to reflect slower total body drug clearance due to slower drug release/absorption from oral formulations. Mechanistic PK models with

  5. Trends in Controlled-Release Oxycodone (Oxycontin[R]) Prescribing among Medicaid Recipients in Kentucky, 1998-2002. Research Note

    ERIC Educational Resources Information Center

    Havens, Jennifer R.; Talbert, Jeffrey C.; Walker, Robert; Leedham, Cynthia; Leukefeld, Carl G.

    2006-01-01

    Context: Prescription opioid abuse has emerged as a public health problem, particularly in rural America. Purpose: To examine temporal and geographic trends in rates of controlled-release oxycodone (OxyContin) prescribing for Kentucky Medicaid recipients. Methods: A cross-sectional analysis was completed in which the state was divided into 3…

  6. Controlled release formulation of oxycodone in patients with moderate to severe chronic osteoarthritis: a critical review of the literature

    PubMed Central

    Taylor, Robert; Raffa, Robert B; Pergolizzi, Joseph V

    2012-01-01

    Osteoarthritis (OA) is a physically and emotionally debilitating disease that predominantly affects the aging adult population. Current pharmacologic treatment options primarily consist of nonsteroidal anti-inflammatory drugs and/or acetaminophen, but associated side effects, analgesic limitations, especially in the elderly, and the need for around-the-clock analgesia have led physicians to search for alternative analgesics. Opioids have shown effectiveness at mitigating both chronic cancer and noncancer pain, and their ability to be placed into controlled release (CR) formulations suggests that they may prove efficacious for OA patients. One formulation, oxycodone CR, has shown effectiveness in cancer pain patients and in some trials of noncancer low back pain. In this review, the objective was to synthesize the reported findings by researchers in this field and present an up-to-date look at the efficacy, safety, and tolerability of oxycodone CR in OA patients. Public literature databases were searched using specific keywords (eg, oxycodone CR) for studies assessing the efficacy and safety profile of oxycodone CR and its use in patients with OA. A total of eleven articles that matched the criteria were identified, which included three placebo-controlled trials, six comparative trials, one pharmacokinetic study in the elderly, and one long-term safety trial. Analysis of the studies revealed that oxycodone CR is reasonably efficacious, safe, and tolerable when used to manage moderate to severe chronic OA pain, with similar side effects to that of other opioids. PMID:22570559

  7. Reformulation of controlled-release oxycodone and pharmacy dispensing patterns near the US–Canada border

    PubMed Central

    Gomes, Tara; Paterson, J Michael; Juurlink, David N; Dhalla, Irfan A; Mamdani, Muhammad M

    2012-01-01

    Background In August 2010, a tamper-resistant formulation of controlled-release oxycodone (OxyContin-OP) was introduced in the United States but not in Canada. Our objective was to determine whether introduction of OxyContin-OP in the United States influenced prescription volumes for the original controlled-release oxycodone formulation (OxyContin) at Canadian pharmacies near the international border. Methods We conducted a population-based, serial, cross-sectional study of prescriptions dispensed from pharmacies in the 3 cities with the highest volume of US–Canada border crossings in Ontario: Niagara Falls, Windsor and Sarnia. We analyzed data on all outpatient prescriptions for OxyContin dispensed by Canadian pharmacies near each border crossing between 2010 Apr. 1 and 2012 Feb. 29. We calculated and compared monthly prescription rates, adjusted per 1000 population and stratified by tablet strength. Results The number of tablets dispensed near 4 border crossings in the 3 Canadian cities remained stable over the study period. However, the rate of dispensing at pharmacies near the Detroit–Windsor Tunnel increased roughly 4-fold between August 2010 and February 2011, from 505 to 1969 tablets per 1000 population. By April 2011, following warnings to prescribers and pharmacies regarding drug-seeking behaviour, the dispensing rate declined to 1683 tablets per 1000 population in this area. By November 2011, the rate had returned to levels observed in early 2010. Our analyses suggest that 242 075 excess OxyContin tablets were dispensed near the Detroit–Windsor Tunnel between August 2010 and October 2011. Conclusions Prescribing of the original formulation of controlled-release oxycodone rose substantially near a major international border crossing following the introduction of a tamper-resistant formulation in the United States. It is possible that the restriction of this finding to the area surrounding the Detroit–Windsor Tunnel reflects specific

  8. Oxycodone

    MedlinePlus

    ... tablets, extended-release capsules, and concentrated solution should only be used to treat people who are tolerant ( ... XR, others); aspirin (Percodan); and ibuprofen. This monograph only includes information about the use of oxycodone alone. ...

  9. Intranasal administration of crushed ALO-02 (extended-release oxycodone with sequestered naltrexone): A randomized, controlled abuse-potential study in nondependent recreational opioid users.

    PubMed

    Setnik, Beatrice; Bramson, Candace; Bass, Almasa; Levy-Cooperman, Naama; Malhotra, Bimal; Matschke, Kyle; Sommerville, Kenneth W; Wolfram, Gernot; Geoffroy, Pierre

    2015-12-01

    ALO-02 is an abuse-deterrent formulation consisting of capsules filled with pellets of extended-release oxycodone surrounding sequestered naltrexone. This randomized, double-blind, placebo-/active-controlled, 4-way crossover study examined the abuse potential of crushed ALO-02 administered intranasally to healthy, nondependent, recreational opioid users. Following drug discrimination and naloxone challenge, eligible participants (n = 32) entered a 4-way crossover treatment phase: crushed single dose of 1 of 2 placebos, ALO-02 30 mg/3.6 mg (oxycodone/naltrexone) or oxycodone immediate-release (IR) 30 mg. Primary end points were Drug Liking and High, measured on visual analog scales (VAS) summarized as maximum effect (Emax ) and effect occurring over 2 hours postdose (AUE0-2  h ). Crushed ALO-02 resulted in significantly lower scores versus oxycodone IR on Drug Liking (Emax , 60.5 vs 92.8; AUE0-2  h , 105.4 vs 160.0, respectively) and High (Emax , 25.2 vs 86.9; AUE0-2  h , 27.1 vs 136.4, respectively; n = 28; P < .0001). Adverse events occurred most frequently with oxycodone IR, followed by ALO-02, then placebo, and were considered mild and consistent with opioid therapy. Crushed ALO-02 administered intranasally to nondependent recreational opioid users resulted in significantly lower scores on Drug Liking/High VAS and other positive subjective measures versus crushed oxycodone IR, suggesting less abuse potential. Demonstration of actual abuse deterrence in the real world requires further research. PMID:26011742

  10. Synthetic geopolymers for controlled delivery of oxycodone: adjustable and nanostructured porosity enables tunable and sustained drug release.

    PubMed

    Forsgren, Johan; Pedersen, Christian; Strømme, Maria; Engqvist, Håkan

    2011-01-01

    In this article we for the first time present a fully synthetic mesoporous geopolymer drug carrier for controlled release of opioids. Nanoparticulate precursor powders with different Al/Si-ratios were synthesized by a sol-gel route and used in the preparation of different geopolymers, which could be structurally tailored by adjusting the Al/Si-ratio and the curing temperatures. In particular, it was shown that the pore sizes of the geopolymers decreased with increasing Al/Si ratio and that completely mesoporous geopolymers could be produced from precursor particles with the Al/Si ratio 2:1. The mesoporosity was shown to be associated with a sustained and linear in vitro release profile of the opioid oxycodone. A clinically relevant release period of about 12 h was obtained by adjusting the size of the pellets. The easily fabricated and tunable geopolymers presented in this study constitute a novel approach in the development of controlled release formulations, not only for opioids, but whenever the clinical indication is best treated with a constant supply of drugs and when the mechanical stability of the delivery vehicle is crucial. PMID:21423616

  11. Synthetic Geopolymers for Controlled Delivery of Oxycodone: Adjustable and Nanostructured Porosity Enables Tunable and Sustained Drug Release

    PubMed Central

    Forsgren, Johan; Pedersen, Christian; Strømme, Maria; Engqvist, Håkan

    2011-01-01

    In this article we for the first time present a fully synthetic mesoporous geopolymer drug carrier for controlled release of opioids. Nanoparticulate precursor powders with different Al/Si-ratios were synthesized by a sol-gel route and used in the preparation of different geopolymers, which could be structurally tailored by adjusting the Al/Si-ratio and the curing temperatures. In particular, it was shown that the pore sizes of the geopolymers decreased with increasing Al/Si ratio and that completely mesoporous geopolymers could be produced from precursor particles with the Al/Si ratio 2∶1. The mesoporosity was shown to be associated with a sustained and linear in vitro release profile of the opioid oxycodone. A clinically relevant release period of about 12 h was obtained by adjusting the size of the pellets. The easily fabricated and tunable geopolymers presented in this study constitute a novel approach in the development of controlled release formulations, not only for opioids, but whenever the clinical indication is best treated with a constant supply of drugs and when the mechanical stability of the delivery vehicle is crucial. PMID:21423616

  12. [Controlled release oxycodone--a new option in the treatment of severe and very severe pain. Review of studies on neuropathic, physical activity-related and postoperative pain].

    PubMed

    Stiehl, M

    2004-08-01

    Opioids are used not only in the treatment of cancer pain, but also pain of non-malignant genesis. In recent years, the efficacy of controlled release (CR) oxycodone in the treatment of the above-mentioned types of pain has been investigated in a number of clinical studies. The present article reviews the clinical studies that have been already published. Thanks to its outstanding pharmacological and pharmacodynamic properties, CR oxycodone is fast acting and brings about long lasting pain relief, coupled with benefits for physical and mental activities. This results in a significant quality-of-life improvement. Oral therapy with CR oxycodone is safe and can be precisely controlled. Since there are no clinical relevant metabolites, there is no danger of accumulation in patients with renal infarction due to these metabolites. Side effects are those typical for opioids, and are readily manageable. CR oxycodone is a good alternative in the treatment of non-cancer pain and can be recommended as first-line treatment for the above-mentioned indications. PMID:16739361

  13. Sustained safety and efficacy of once-daily hydromorphone extended-release (OROS® hydromorphone ER) compared with twice-daily oxycodone controlled-release over 52 weeks in patients with moderate to severe chronic noncancer pain.

    PubMed

    Richarz, Ute; Waechter, Sandra; Sabatowski, Rainer; Szczepanski, Leszek; Binsfeld, Heinrich

    2013-01-01

    Once-daily hydromorphone extended-release (OROS(®) hydromorphone ER) and oxycodone controlled-release (CR) are semisynthetic, ER opioid analgesics with established efficacy. An open-label, randomized, 24-week, parallel group, flexible-dose study demonstrated noninferiority of OROS hydromorphone ER vs. twice-daily oxycodone CR in patients with chronic noncancer pain. In total, 112 patients were enrolled in a 28-week, open-label extension study; 60 patients received OROS hydromorphone ER and 52 received oxycodone CR. The primary efficacy measure was the change from baseline to Weeks 38 and 52 in Brief Pain Inventory item "pain right now." Global assessments of efficacy, dosing convenience, and tolerability were secondary endpoints. Mean change in "pain right now" from baseline to Week 38 was -3.0 (OROS hydromorphone ER) vs. -2.8 (oxycodone CR), and from baseline to Week 52 was -2.9 vs. -2.8; these changes were similar to the changes in the core phase (-2.1 vs. -2.1). Similar improvements were demonstrated for secondary assessments, including pain, pain interference, and quality of life. At Week 52, global assessment of efficacy was rated as "very good" or "good" by the majority of patients (OROS hydromorphone ER, 91.7%; oxycodone CR, 86.5%). More patients in the OROS hydromorphone ER group (35.0% vs. 21.2%) assessed mode of drug intake as "very convenient." The majority of patients receiving OROS hydromorphone ER (88.3%) and oxycodone CR (88.5%) rated tolerability as "good" or "very good" at Week 52; few patients discontinued treatment because of an adverse event (1.6% vs. 0.4%, respectively). The effectiveness of OROS hydromorphone ER and oxycodone CR was maintained through 1 year. PMID:22510252

  14. Oxycodone

    MedlinePlus

    ... this type of medication for at least one week. Oxycodone is in a class of medications called ... have stopped taking them within the past two weeks: isocarboxazid (Marplan), linezolid (Zyvox), methylene blue, phenelzine (Nardil), ...

  15. [Sustained-release Opioids: Morphine, Oxycodone and Tapentadol].

    PubMed

    Takahashi, Yoshika; Iseki, Masako

    2015-11-01

    Opioid analgesics are widely used for managing moderate to severe pain. In cancer pain management sustained-release opioids are used for continuous pain as well as immediate-release opioids for breakthrough pain. Sustained-release drugs have the advantage of stabilizing the blood concentration, although it takes some time to exert their effects. In Japan, the currently available oral sustained-release opioids include six types of sustained-release morphine (three are once-a-day formulations, while the rest are twice-a-day), one type of oxycodone and tapentadol. In this article, we will discuss the pharmacokinetic properties of MS Contin, Morphes, Kadian, P guard and Pacif as sustained-release morphine, Oxycontin as sustained-release oxycodone and Tapenta as sustained-release tapentadol. PMID:26689063

  16. Pain therapy with oxycodone/naloxone prolonged-release combination: case report.

    PubMed

    Błaszczyk, Feliks; Droń, Aleksandra

    2013-01-01

    Pain afflicts patients suffering from many chronic diseases and is present in 80% of cases of patients with advanced cancer who suffer from persistent pain. The aim of the pain treatment is to achieve the maximum analgesic effect while minimizing side effects. The main analgesic agent - morphine is unfortunately a therapy associated with gastrointestinal side effects. It appears that the combination of oxycodone and naloxone available as Targin(®) (Mundipharma) is an alternative. The paper presents a case of a 45-year-old patient who was treated effectively with oxycodone/naloxone prolonged-release tablets. This treatment has proven to be effective in providing pain and constipation control. PMID:24592131

  17. Randomized, double-blind, placebo-controlled and active-controlled study to assess the relative abuse potential of oxycodone HCl-niacin tablets compared with oxycodone alone in nondependent, recreational opioid users

    PubMed Central

    Webster, Lynn R; Rolleri, Robert L; Pixton, Glenn C; Sommerville, Kenneth W

    2012-01-01

    Background Abuse-deterrent formulations attempt to address public health and societal concerns regarding opioid abuse. Oxycodone HCl-niacin tablets combine oxycodone HCl with niacin and functional inactive excipients to create potential barriers to oral, intranasal, and intravenous abuse. This study compared the relative abuse potential of oral immediate-release oxycodone HCl-niacin with that of oral immediate-release oxycodone HCl and placebo in nondependent, recreational opioid users. Methods Forty-nine participants received oxycodone HCl-niacin 40/240 mg and 80/480 mg, oxycodone 40 mg and 80 mg, and placebo in a randomized, double-blind, placebo-controlled and active-controlled, five-way crossover study. Primary endpoints based on a bipolar 100 mm visual analog scale for drug liking were area under effect curve (AUE0–1h, AUE0–2h, AUE0–3h), peak disliking, and effect at 0.5 hours post-dose (E0.5h). Other endpoints included take drug again assessment, overall drug liking, and pupillometry. Results There were statistically significant differences between oxycodone HCl-niacin and oxycodone HCl doses for all primary endpoints (P < 0.0001, all comparisons), suggesting reduced abuse potential with oxycodone HCl-niacin. Take drug again and overall drug liking showed greater liking of oxycodone alone. Oxycodone HCl-niacin 80/480 mg had consistently lower liking assessments than oxycodone HCl-niacin 40/240 mg, suggesting a dose-response to the aversive effects of niacin. Opioid-related adverse events were similar for equivalent oxycodone doses. The treatment-emergent adverse events most specifically associated with oxycodone HCl-niacin (ie, skin-burning sensation, warmth, and flushing) were consistent with the expected vasocutaneous effects of niacin. No serious adverse events were reported. Conclusion Oxycodone HCl-niacin tablets may, in a dose-dependent manner, decrease the potential for oral abuse of oxycodone without unexpected adverse events or clinically

  18. Pain therapy with oxycodone/naloxone prolonged-release combination: case report

    PubMed Central

    Droń, Aleksandra

    2013-01-01

    Pain afflicts patients suffering from many chronic diseases and is present in 80% of cases of patients with advanced cancer who suffer from persistent pain. The aim of the pain treatment is to achieve the maximum analgesic effect while minimizing side effects. The main analgesic agent – morphine is unfortunately a therapy associated with gastrointestinal side effects. It appears that the combination of oxycodone and naloxone available as Targin® (Mundipharma) is an alternative. The paper presents a case of a 45-year-old patient who was treated effectively with oxycodone/naloxone prolonged-release tablets. This treatment has proven to be effective in providing pain and constipation control. PMID:24592131

  19. Intractable restless legs syndrome: role of prolonged-release oxycodone-naloxone.

    PubMed

    de Biase, Stefano; Valente, Mariarosaria; Gigli, Gian Luigi

    2016-01-01

    Restless legs syndrome (RLS) is a common neurological disorder characterized by an irresistible urge to move the legs accompanied by uncomfortable sensations that occur at night or at time of rest. Pharmacological therapy should be limited to patients who suffer from clinically relevant symptoms. Chronic RLS is usually treated with either a dopamine agonist (pramipexole, ropinirole, rotigotine) or an α2δ calcium-channel ligand (gabapentin, gabapentin enacarbil, pregabalin). Augmentation is the main complication of long-term dopaminergic treatment, and frequently requires a reduction of current dopaminergic dose or a switch to non-dopaminergic medications. Opioids as monotherapy or add-on treatment should be considered when alternative satisfactory regimens are unavailable and the severity of symptoms warrants it. In a recent Phase III trial, oxycodone-naloxone prolonged release (PR) demonstrated a significant and sustained effect on patients with severe RLS inadequately controlled by previous treatments. The adverse-event profile was consistent with the safety profile of opioids. The most frequent adverse events were fatigue, constipation, nausea, headache, hyperhidrosis, somnolence, dry mouth, and pruritus. Adverse events were usually mild or moderate in intensity. No cases of augmentation were reported. Oxycodone-naloxone PR is approved for the second-line symptomatic treatment of adults with severe to very severe idiopathic RLS after failure of dopaminergic treatment. Further studies are needed to evaluate if oxycodone-naloxone PR is equally efficacious as a first-line treatment. Moreover, long-term comparative studies between opioids, dopaminergic drugs and α2δ ligands are needed. PMID:26966363

  20. Profile of extended-release oxycodone/acetaminophen for acute pain

    PubMed Central

    Bekhit, Mary Hanna

    2015-01-01

    This article provides a historical and pharmacological overview of a new opioid analgesic that boasts an extended-release (ER) formulation designed to provide both immediate and prolonged analgesia for up to 12 hours in patients who are experiencing acute pain. This novel medication, ER oxycodone/acetaminophen, competes with current US Food and Drug Administration (FDA)-approved opioid formulations available on the market in that it offers two benefits concurrently: a prolonged duration of action, and multimodal analgesia through a combination of an opioid (oxycodone) with a nonopioid component. Current FDA-approved combination analgesics, such as Percocet (oxycodone/acetaminophen), are available solely in immediate-release (IR) formulations. PMID:26527898

  1. Role of oxycodone and oxycodone/naloxone in cancer pain management.

    PubMed

    Leppert, Wojciech

    2010-01-01

    Oxycodone is a valued opioid analgesic, which may be administered either as the first strong opioid or when other strong opioids are ineffective. In case of insufficient analgesia and/or intense adverse effects such as sedation, hallucinations and nausea/vomiting a switch from another opioid to oxycodone might be beneficial. Oxycodone is administered to opioid-naive patients with severe pain and to patients who were unsuccessfully treated with weak opioids, namely tramadol, codeine and dihydrocodeine. Oxycodone effective analgesia may be attributed to its affinity to μ and possibly κ opioid receptors, rapid penetration through the blood-brain barrier and higher concentrations in brain than in plasma. Oxycodone displays high bioavailability after oral administration and may be better than morphine in patients with renal impairment due to the decreased production of active metabolites. Recently an oral controlled-release oxycodone formulation was introduced in Poland. Another new product that was launched recently is a combination of prolonged-release oxycodone with prolonged-release naloxone (oxycodone/naloxone tablets). The aim of this review is to outline the pharmacodynamic and pharmacokinetic properties, drug interactions, dosing rules, adverse effects, equianalgesic dose ratio with other opioids and clinical studies of oxycodone in patients with cancer pain. The potential role of oxycodone/naloxone in chronic pain management and its impact on the bowel function is also discussed. PMID:20884999

  2. A randomized double-blind, placebo-controlled efficacy and safety study of ALO-02 (extended-release oxycodone surrounding sequestered naltrexone) for moderate-to-severe chronic low back pain treatment.

    PubMed

    Rauck, Richard L; Hale, Martin E; Bass, Almasa; Bramson, Candace; Pixton, Glenn; Wilson, Jacquelyn G; Setnik, Beatrice; Meisner, Paul; Sommerville, Kenneth W; Malhotra, Bimal K; Wolfram, Gernot

    2015-09-01

    The objective of this multicenter, double-blind, placebo-controlled, randomized withdrawal study was to evaluate the efficacy and safety of ALO-02, an abuse-deterrent formulation containing pellets of extended-release oxycodone hydrochloride (HCl) surrounding sequestered naltrexone HCl, compared with placebo in the treatment of moderate-to-severe chronic low back pain. An open-label titration period in which all patients received ALO-02 was followed by a double-blind treatment period where patients meeting treatment response criteria were randomized to either a fixed dose of ALO-02 or placebo. Daily average low back pain was assessed using an 11-point numeric rating scale (NRS)-Pain. Of the 663 patients screened, 410 received ALO-02 during the open-label conversion and titration period and 281 patients were randomized to the double-blind treatment period (n = 134, placebo; n = 147, ALO-02). Change in the mean NRS-Pain score from randomization baseline to the final 2 weeks of the treatment period was significantly different favoring ALO-02 compared with placebo (P = 0.0114). Forty-four percent of patients treated with placebo and 57.5% of patients treated with ALO-02 reported ≥30% improvement in weekly average NRS-Pain scores from screening to the final 2 weeks of the treatment period (P = 0.0248). In the double-blind treatment period, 56.8% of patients in the ALO-02 group and 56.0% of patients in the placebo group experienced a treatment-emergent adverse event (TEAE). The most common treatment-related TEAEs for ALO-02 during the treatment period were nausea, vomiting, and constipation, consistent with opioid therapy. ALO-02 has been demonstrated to provide significant reduction of pain in patients with chronic low back pain and has a safety profile similar to other opioids. PMID:25993547

  3. Comparison of oxycodone and fentanyl for postoperative patient-controlled analgesia after laparoscopic gynecological surgery

    PubMed Central

    Park, Joong-Ho; Lee, Chiu; Shin, Youngmin; Ban, Jong-Seouk; Lee, Ji-Hyang

    2015-01-01

    Background Opioids are widely used in boluses and patient-controlled analgesia (PCA) for postoperative pain control. In this study, we compared the effects of oxycodone and fentanyl on postoperative pain in patients with intravenous patient-controlled analgesia (IV-PCA) after laparoscopic gynecological surgery. Methods Seventy-four patients undergoing elective total laparoscopic hysterectomy or laparoscopic myomectomy were randomly assigned to the administration of either fentanyl or oxycodone using IV-PCA (potency ratio 1 : 60). The cumulative dose administered in the patient-controlled mode during the initial 48 hours after the operation was measured. Patients were also assessed for postoperative pain severity, adverse effects, and patient satisfaction. Results No significant differences were observed in patient satisfaction with the analgesia during the postoperative period. Patients in the oxycodone group experienced significantly more dizziness compared to the fentanyl group. Patients in the oxycodone group showed significantly lower consumption of opioid in the patient-controlled mode (10.1 ± 8.5 ml vs. 16.6 ± 12.0 ml, P = 0.013). Conclusions Our data suggest that oxycodone and fentanyl demonstrated similar effects, and therefore oxycodone may be a good alternative to fentanyl in postoperative pain management. Further studies in various clinical settings will be needed to determine the adequate potency ratio. PMID:25844134

  4. The effects of CYP2D6 and CYP3A activities on the pharmacokinetics of immediate release oxycodone

    PubMed Central

    Samer, CF; Daali, Y; Wagner, M; Hopfgartner, G; Eap, CB; Rebsamen, MC; Rossier, MF; Hochstrasser, D; Dayer, P; Desmeules, JA

    2010-01-01

    Background and purpose: There is high interindividual variability in the activity of drug-metabolizing enzymes catalysing the oxidation of oxycodone [cytochrome P450 (CYP) 2D6 and 3A], due to genetic polymorphisms and/or drug–drug interactions. The effects of CYP2D6 and/or CYP3A activity modulation on the pharmacokinetics of oxycodone remains poorly explored. Experimental approach: A randomized crossover double-blind placebo-controlled study was performed with 10 healthy volunteers genotyped for CYP2D6 [six extensive (EM), two deficient (PM/IM) and two ultrarapid metabolizers (UM)]. The volunteers randomly received on five different occasions: oxycodone 0.2 mg·kg−1 and placebo; oxycodone and quinidine (CYP2D6 inhibitor); oxycodone and ketoconazole (CYP3A inhibitor); oxycodone and quinidine+ketoconazole; placebo. Blood samples for plasma concentrations of oxycodone and metabolites (oxymorphone, noroxycodone and noroxymorphone) were collected for 24 h after dosing. Phenotyping for CYP2D6 (with dextromethorphan) and CYP3A (with midazolam) were assessed at each session. Key results: CYP2D6 activity was correlated with oxymorphone and noroxymorphone AUCs and Cmax (−0.71 < Spearman correlation coefficient ρs < −0.92). Oxymorphone Cmax was 62% and 75% lower in PM than EM and UM. Noroxymorphone Cmax reduction was even more pronounced (90%). In UM, oxymorphone and noroxymorphone concentrations increased whereas noroxycodone exposure was halved. Blocking CYP2D6 (with quinidine) reduced oxymorphone and noroxymorphone Cmax by 40% and 80%, and increased noroxycodone AUC∞ by 70%. Blocking CYP3A4 (with ketoconazole) tripled oxymorphone AUC∞ and reduced noroxycodone and noroxymorphone AUCs by 80%. Shunting to CYP2D6 pathway was observed after CYP3A4 inhibition. Conclusions and implications: Drug–drug interactions via CYP2D6 and CYP3A affected oxycodone pharmacokinetics and its magnitude depended on CYP2D6 genotype. PMID:20590587

  5. Oxycodone with an opioid receptor antagonist: A review.

    PubMed

    Davis, Mellar P; Goforth, Harold W

    2016-01-01

    The rationale for putting opioid antagonists with an agonist is to improve pain control, to reduce side effects, and/or to reduce abuse. The combination of prolonged release (PR) oxycodone and naloxone reduces constipation as demonstrated in multiple studies and has been designated a tamper-resistant opioid by the Food and Drug Administration. Bioequivalence of the combination product compared with PR oxycodone has not been established. Several of the pivotal studies provided suboptimal laxative support in the control arm of the randomized trials. Two noninferiority trials have demonstrated equivalent analgesia between PR oxycodone and the combination product at doses of less than 120 mg of oxycodone per day. There appears to be an analgesic ceiling above 80-120 mg of oxycodone per day. Safety monitoring during randomized trials was not been well described in published manuscripts. Benefits appear to be better for those with chronic noncancer pain compared with individuals with cancer when constipation was the primary outcome. PMID:26908305

  6. Pooled post hoc analysis of population pharmacokinetics of oxycodone and acetaminophen following a single oral dose of biphasic immediate-release/extended-release oxycodone/acetaminophen tablets

    PubMed Central

    Franke, Ryan M; Morton, Terri; Devarakonda, Krishna

    2015-01-01

    This analysis evaluated the single-dose population pharmacokinetics (PK) of biphasic immediate-release (IR)/extended-release (ER) oxycodone (OC)/acetaminophen (APAP) 7.5/325 mg tablets administered under fasted conditions and the effects of a meal on their single-dose population PK. Data were pooled from four randomized, single-dose crossover trials enrolling healthy adult (18–55 years old) participants (three trials) and nondependent recreational users of prescription opioids (one trial) with a body weight of ≥59 kg. Participants received IR/ER OC/APAP 7.5/325 mg tablets in single doses of 7.5/325 mg (one tablet), 15/650 mg (two tablets), or 30/1,300 mg (four tablets) under fasted or fed conditions. Six variables were examined: sex, race, age, weight, height, and body mass index. Single-dose population PK was analyzed using first-order conditional estimation methods. A total of 151 participants were included in the analysis under fasted conditions, and 31 participants were included in the fed analysis. Under fasted conditions, a 10% change in body weight was accompanied by ~7.5% change in total body clearance (CL/F) and volume of distribution (V/F) of OC and APAP. Black participants had 17.3% lower CL/F and a 16.9% lower V/F of OC compared with white participants. Under fed conditions, the absorption rate constant of OC and APAP decreased significantly, although there was no effect on CL/F and V/F. Considering that the recommended dose for IR/ER OC/APAP 7.5/325 mg tablets is two tablets every 12 hours, adjustments of <50% are not clinically relevant. Dose adjustment may be necessary for large deviations from average body weight, but the small PK effects associated with race and consumption of a meal are not clinically relevant. PMID:26316698

  7. Pooled post hoc analysis of population pharmacokinetics of oxycodone and acetaminophen following a single oral dose of biphasic immediate-release/extended-release oxycodone/acetaminophen tablets.

    PubMed

    Franke, Ryan M; Morton, Terri; Devarakonda, Krishna

    2015-01-01

    This analysis evaluated the single-dose population pharmacokinetics (PK) of biphasic immediate-release (IR)/extended-release (ER) oxycodone (OC)/acetaminophen (APAP) 7.5/325 mg tablets administered under fasted conditions and the effects of a meal on their single-dose population PK. Data were pooled from four randomized, single-dose crossover trials enrolling healthy adult (18-55 years old) participants (three trials) and nondependent recreational users of prescription opioids (one trial) with a body weight of ≥59 kg. Participants received IR/ER OC/APAP 7.5/325 mg tablets in single doses of 7.5/325 mg (one tablet), 15/650 mg (two tablets), or 30/1,300 mg (four tablets) under fasted or fed conditions. Six variables were examined: sex, race, age, weight, height, and body mass index. Single-dose population PK was analyzed using first-order conditional estimation methods. A total of 151 participants were included in the analysis under fasted conditions, and 31 participants were included in the fed analysis. Under fasted conditions, a 10% change in body weight was accompanied by ~7.5% change in total body clearance (CL/F) and volume of distribution (V/F) of OC and APAP. Black participants had 17.3% lower CL/F and a 16.9% lower V/F of OC compared with white participants. Under fed conditions, the absorption rate constant of OC and APAP decreased significantly, although there was no effect on CL/F and V/F. Considering that the recommended dose for IR/ER OC/APAP 7.5/325 mg tablets is two tablets every 12 hours, adjustments of <50% are not clinically relevant. Dose adjustment may be necessary for large deviations from average body weight, but the small PK effects associated with race and consumption of a meal are not clinically relevant. PMID:26316698

  8. Comparative Cognitive and Subjective Side Effects of Immediate Release Oxycodone in Healthy Middle Age and Older Adults

    PubMed Central

    Cherrier, M.; Amory, J.; Ersek, M.; Risler, L.; Shen, D.

    2009-01-01

    This study measured the objective and subjective neurocognitive effects of a single 10mg dose of immediate-release oxycodone in healthy, older (>65 years) and middle age (35 – 55 years) adults who were not suffering from chronic or significant daily pain. Seventy-one participants completed two separate study days and were blind to medication condition (placebo, 10 mg oxycodone). Plasma oxycodone concentration peaked between 60 and 90 min post dose (p<0.01) and pupil size, an indication of physiological effects of the medication peaked at approximately 90 to 120 min post dose (p<0.01). Significant declines in simple and sustained attention, working memory and verbal memory were observed at one hour post dose compared to baseline for both age groups with a trend toward return to baseline by five hours post dose. For almost all cognitive measures there were no medication by age interaction effects, which indicates that the two age groups exhibited a similar responses to the medication challenge. This study suggests that for healthy older adults who are not suffering from chronic pain, neurocognitive and pharmacodynamic changes in response to a 10 mg dose of immediate release oxycodone are similar to those observed for middle age adults. Perspective Study findings indicate that the metabolism, neurocognitive effects, and physical side effects of oral oxycodone are similar for healthy middle-age and older adults. Therefore, clinicians should not avoid prescribing oral opioids to older adults based on the belief that older adults are at higher risk for side effects than younger adults. PMID:19729346

  9. Comparison of the analgesic effect of patient-controlled oxycodone and fentanyl for pain management in patients undergoing colorectal surgery.

    PubMed

    Jung, Kyeo-Woon; Kang, Hyeon-Wook; Park, Chan-Hye; Choi, Byung-Hyun; Bang, Ji-Yeon; Lee, Soo-Han; Lee, Eun-Kyung; Choi, Byung-Moon; Noh, Gyu-Jeong

    2016-08-01

    Oxycodone is a μ-opioid receptor agonist and is generally indicated for the relief of moderate to severe pain. The aim of this study was to compare the analgesic efficacy of patient-controlled oxycodone and fentanyl for postoperative pain in patients undergoing colorectal surgery. Patients scheduled to undergo elective colorectal surgery (n=82) were allocated to receive oxycodone (n=41, concentration of 1 mg/mL) or fentanyl (n=41, concentration of 15 μg/mL) for postoperative pain management. After the operation, pain using a numerical rating scale (NRS), delivery to demand ratio, infused dose of patient-controlled analgesia (PCA), side effects, and sedation levels were evaluated. Median (25%-75%) cumulative PCA dose of oxycodone group at 48 hours (66.9, 58.4-83.7 mL) was significantly less than that of fentanyl group (80.0, 63.4-103.3 mL, P=.037). Six hours after surgery, the mean (SD) NRS scores of the oxycodone and fentanyl groups were 6.2 (2.4) and 6.8 (1.9), respectively (P=.216). The mean equianalgesic potency ratio of oxycodone to fentanyl was 55:1. The groups did not differ in postoperative nausea, vomiting, and level of sedation. Patient-controlled oxycodone provides similar effects for pain relief compared to patient-controlled fentanyl in spite of less cumulative PCA dose. Based on these results, oxycodone can be a useful alternative to fentanyl for PCA in patients after colorectal surgery. PMID:27128496

  10. Comparison of epidural oxycodone and epidural morphine for post-caesarean section analgesia: A randomised controlled trial

    PubMed Central

    Sng, Ban Leong; Kwok, Sarah Carol; Mathur, Deepak; Ithnin, Farida; Newton-Dunn, Clare; Assam, Pryseley Nkouibert; Sultana, Rehena; Sia, Alex Tiong Heng

    2016-01-01

    Background and Aims: Epidural morphine after caesarean section may cause moderate to severe pruritus in women. Epidural oxycodone has been shown in non-obstetric trials to reduce pruritus when compared to morphine. We hypothesised that epidural oxycodone may reduce pruritus after caesarean section. Methods: A randomised controlled trial was conducted in pregnant women at term who underwent caesarean section with combined spinal-epidural technique initiated with intrathecal fentanyl 15 μg. Women received either epidural morphine 3 mg or epidural oxycodone 3 mg via the epidural catheter after delivery. The primary outcome was the incidence of pruritus at 24 h after caesarean section. The secondary outcomes were the pruritus scores, treatment for post-operative nausea and vomiting (PONV), pain scores and maternal satisfaction. Results: One hundred women were randomised (group oxycodone O = 50, morphine M = 50). There was no difference between Group O and M in the incidence of pruritus (n [%] 28 [56%] vs. 31 [62%], P = 0.68) and the worst pruritus scores (mean [standard deviation] 2.6 (2.8) vs. 3.3 [3.1], P = 0.23), respectively. Both groups had similar pain scores at rest (2.7 [2.3] vs. 2.0 [2.7], P = 0.16) and sitting up (5.0 [2.3] vs. 4.6 [2.4], P = 0.38) at 24 h. Pruritus scores were lower at 4–8, 8–12 and 12–24 h with oxycodone, but pain scores were higher. Both groups had a similar need for treatment of PONV and maternal satisfaction with analgesia. Conclusion: There was no difference in the incidence of pruritus at 24 h between epidural oxycodone and morphine. However, pruritus scores were lower with oxycodone between 4 and 24 h after surgery with higher pain scores in the same period. PMID:27053782

  11. Oxycodone/Naloxone PR: A Review in Severe Refractory Restless Legs Syndrome.

    PubMed

    Frampton, James E

    2015-06-01

    An oral, fixed-dose combination of prolonged-release (PR) oxycodone with PR naloxone (Targin(®), Targiniq(®), Targinact(®); hereafter referred to as oxycodone/naloxone PR) is approved in Europe for the second-line symptomatic treatment of patients with severe to very severe idiopathic restless legs syndrome (RLS), after failure of dopaminergic therapy. Coadministration of naloxone represents a targeted approach to counteracting opioid-induced bowel dysfunction without compromising therapeutic efficacy; because of its very low oral bioavailability, naloxone blocks the action of oxycodone at opioid receptors locally in the gut. The efficacy of oxycodone/naloxone PR in patients with severe RLS inadequately controlled by previous (mainly dopaminergic) treatment has been demonstrated in RELOXYN, a 12-week, randomized, double-blind study with a 40-week open-label extension. In this pivotal study, oxycodone/naloxone PR significantly improved RLS symptoms compared with placebo from week 2 onwards; a beneficial effect of oxycodone/naloxone PR was maintained through 1 year of treatment. Furthermore, improvements in RLS symptoms in oxycodone/naloxone PR recipients were accompanied by similarly sustained improvements in disease-specific quality of life and subjective sleep variables. Oxycodone/naloxone PR was generally well tolerated, with a treatment-related adverse event profile (e.g. gastrointestinal disorders, CNS disorders, fatigue and pruritus) that was consistent with that expected for opioid therapy. Notably, there were no confirmed cases of augmentation among oxycodone/naloxone PR recipients throughout the course of the study. Results from the well-designed RELOXYN trial have thus demonstrated the value of oxycodone/naloxone PR as a second-line therapy for severe refractory RLS; further investigation of this combination product as a first-line treatment for severe RLS is now warranted. PMID:26135898

  12. The Adverse Events of Oxycodone in Cancer-Related Pain: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

    PubMed

    Ma, Hu; Liu, Yuan; Huang, Lang; Zeng, Xian-Tao; Jin, Su-Han; Yue, Guo-Jun; Tian, Xu; Zhou, Jian-Guo

    2016-04-01

    The adverse events (AEs) of oxycodone in cancer-related pain were controversial, so we conducted a meta-analysis to determine it.PubMed, Embase, CBM, CNKI, WanFang database, The Cochrane library, Web of Science, and the reference of included studies were searched to recognize pertinent studies. Relative risk (RR) with 95% confidence intervals (CIs) for all AEs were all extracted. The fixed-effects model was used to calculate pooled RRs and 95% CIs. Power calculation was performed using macro embedded in SAS software after all syntheses were completed.We identified 11 eligible trials involving 1211 patients: 604 patients included in oxycodone group and 607 patients involved in control group. Our quantitative analysis included 8 AEs, and the pooled analyses indicated that oxycodone compared with other opioids in cancer-related pain were not significantly decreased RRs of all AEs (dizziness RR = 0.94, 95% CI: 0.69-1.30, Z = 0.35, P = 0.72; nausea RR = 0.88, 95% CI: 0.72-1.07, Z = 1.26, P = 0.21; vomiting RR = 0.89, 95% CI: 0.70-1.15, Z = 0.9, P = 0.37; sleepiness RR = 0.86, 95% CI: 0.38-1.36, Z = 0.36, P = 0.72; constipation RR = 0.98, 95% CI: 0.81-1.19, Z = 0.21, P = 0.83; anorexia RR = 0.97, 95% CI = 0.58-1.62, Z = 0.11, P = 0.91; pruritus RR = 0.76, 95% CI: 0.44-1.30, Z = 1.01, P = 0.31; dysuria RR = 0.33, 95% CI: 0.07-1.62, Z = 1.36, P = 0.1)]. The subgroup analysis shown that Ox controlled-release (CR) had less sleepiness compared with MS-contin (Mc) CR (RR = 0.47, 95% CI: 0.25-0.90, P = 0.02). The power analysis suggests that all AEs have low statistical power.The present meta-analysis detected that no statistically significant difference were found among oxycodone and other opioids in all AEs, but Ox CR may had less sleepiness compared with Mc CR when subgroup analysis were conducted. PMID:27082588

  13. Prescription opioids. III. Disposition of oxycodone in oral fluid and blood following controlled single-dose administration.

    PubMed

    Cone, Edward J; DePriest, Anne Z; Heltsley, Rebecca; Black, David L; Mitchell, John M; LoDico, Charles; Flegel, Ron

    2015-04-01

    Oxycodone (OC) is recommended to be included as an analyte tested in the proposed Substance Abuse and Mental Health Services Administration (SAMHSA's) Mandatory Guidelines for Federal Workplace Drug Testing Programs using Oral Fluid (OF) Specimens. This study demonstrates the time course of OC and metabolites, noroxycodone (NOC), oxymorphone (OM) and noroxymorphone (NOM), in near-simultaneous paired OF and whole blood (BL) specimens by liquid chromatography-tandem mass spectrometry (LC-MS-MS) (limit of detection = 1 ng/mL OF, 5 ng/mL BL). A single dose of OC 20 mg controlled-release was administered to 12 healthy subjects followed by specimen collections for 52 h. Analyte prevalence was as follows: OF, OC > NOC > OM; and BL, OC > NOC > NOM. OC and NOC were frequently detected within 15-30 min in OF and 30 min to 2 h in BL. NOM and OM appeared between 1.5-5 h post-dose. The mean OF-to-BL (OF:BL) ratios and correlations were 5.4 for OC (r = 0.719) and 1.0 for NOC (r = 0.651). The period of detection for OF exceeded BL by ∼2-fold at similar cutoff concentrations. At a 1 ng/mL cutoff for OF, the mean detection time was 34 h for OC and NOC. These data provide new information that should facilitate interpretation of OC test results. PMID:25589778

  14. Long-term efficacy and safety of combined prolonged-release oxycodone and naloxone in the management of non-cancer chronic pain

    PubMed Central

    Sandner-Kiesling, A; Leyendecker, P; Hopp, M; Tarau, L; Lejcko, J; Meissner, W; Sevcik, P; Hakl, M; Hrib, R; Uhl, R; Dürr, H; Reimer, K

    2010-01-01

    Objective: The aim of this study was to assess safety and efficacy of fixed combination oxycodone prolonged release (PR)/naloxone PR in terms of both analgesia and improving opioid-induced bowel dysfunction (OIBD) and associated symptoms, such as opioid-induced constipation (OIC), in adults with chronic non-cancer pain. Study design: These were open-label extension studies in which patients who had previously completed a 12-week, double-blind study received oxycodone PR/naloxone PR for up to 52 weeks. The analgesia study assessed pain using the modified Brief Pain Inventory-Short Form (BPI-SF). The bowel function study assessed improvements in constipation using the Bowel Function Index (BFI). Results: At open-label baseline in the analgesia study (n = 379), mean score [± standard deviation (SD)] for the BPI-SF item ‘average pain over the last 24 h’ was 3.9 ± 1.52, and this remained low at 6 months (3.7 ± 1.59) and 12 months (3.8 ± 1.72). Mean scores for BPI-SF item ‘sleep interference’, and the BPI-SF ‘pain’ and ‘interference with activities’ subscales also remained low throughout the 52-week study. In the bowel function study (n = 258), mean BFI score (± SD) decreased from 35.6 ± 27.74 at the start of the extension study to 20.6 ± 24.01 after 12 months of treatment with oxycodone PR/naloxone PR. Pain scores also remained low and stable during this study. Adverse events in both extension phases were consistent with those associated with opioid therapy; no additional safety concerns were observed. Conclusion: Results from these two open-label extension studies demonstrate the long-term efficacy and tolerability of fixed combination oxycodone PR/naloxone PR in the treatment of chronic pain. Patients experienced clinically relevant improvements in OIBD while receiving effective analgesic therapy. PMID:20370845

  15. A Randomized, Double-Blind, Double-Dummy Study to Evaluate the Intranasal Human Abuse Potential and Pharmacokinetics of a Novel Extended-Release Abuse-Deterrent Formulation of Oxycodone

    PubMed Central

    Kopecky, Ernest A.; Smith, Michael D.; Fleming, Alison B.

    2016-01-01

    Objective. Evaluate the human abuse potential (HAP) of an experimental, microsphere-in-capsule formulation of extended-release oxycodone (oxycodone DETERx®) (herein “DETERx”). Design. Randomized, double-blind, double-dummy, positive- and placebo-controlled, single-dose, four-phase, four-treatment, crossover study. Setting. Clinical research site. Subjects. There were 39 qualifying subjects (72% male, 85% white, mean age of 27 years) with 36 completing all four Double-blind Treatment Periods. Methods. The four phases encompassed: 1) Screening; 2) Drug Discrimination; 3) Double-blind Treatment; and 4) Follow-up. Drug Discrimination tests ensured that subjects could distinguish placebo from opioid. The four Double-blind Treatments compared DETERx—administered as either a crushed intranasal (IN) or an intact oral (PO) preparation—with immediate-release oxycodone IN (OXY-IR IN) and with an intact IN and PO placebo DETERx control. Results. For primary pharmacokinetic (PK) assessments, abuse quotient (Cmax/Tmax) was lower with DETERx IN than DETERx PO; both treatments were substantially lower than OXY-IR IN (6.24, 8.60, and 69.6 ng/mL/h, respectively). For drug liking, the primary subjective pharmacodynamic (PD) endpoint, both DETERx IN and DETERx PO produced significantly lower scores than OXY-IR IN (P ≤ 0.0001 for each); DETERx IN was less liked than DETERx PO (P ≤ 0.05), mirroring the PK relationships. Objectively assessed pupillometry corroborated the more rapid and significantly greater effect of OXY-IR IN than either DETERx IN or DETERx PO (P ≤ 0.007 for each). Overall safety profiles of DETERx and OXY-IR were comparable and both were well tolerated. Conclusions. Pharmacokinetic and pharmacodynamic outcomes suggest that DETERx IN has relatively low HAP; continued research in larger populations is suggested. PMID:26814256

  16. Low-dose oral prolonged-release oxycodone/naloxone for chronic pain in elderly patients with cognitive impairment: an efficacy–tolerability pilot study

    PubMed Central

    Petrò, Emiliano; Ruffini, Elena; Cappuccio, Melania; Guerini, Valeria; Belotti, Gloria; Fascendini, Sara; Licini, Cristina; Marcassa, Claudio

    2016-01-01

    Objective This pilot study evaluated the efficacy and safety of prolonged-release oxycodone/naloxone (OXN-PR) in older subjects with chronic pain and mild-to-moderate cognitive impairment. Methods This was a prospective, observational, open-label study of 45-day duration. Patients with moderate-to-severe chronic pain and naïve to strong opioids were recruited from nursing homes and Alzheimer’s disease centers. OXN-PR was initiated at low doses (5 mg od or bid) and increased to a maximum of 20 mg bid. The primary efficacy endpoint was a pain intensity reduction of ≥30% from baseline (T0) to 15 days after OXN-PR initiation, as assessed by a numerical rating scale or the Pain Assessment in Advanced Dementia scale. Other assessments included the Barthel activities of daily living index, Neuropsychiatric Inventory, Bowel Function Index, and adverse events. Results The analysis included 53 patients (mean age, 83.0 years; mean Mini-Mental State Examination score, 18.6) with severe pain (median Numerical Rating Scale/Pain Assessment in Advanced Dementia 6) and substantial impairment in daily functioning (mean Barthel index, 32.2). The primary endpoint was achieved by 92.4% of patients. OXN-PR significantly reduced mean pain intensity from baseline to study end (numerical rating scale, 6.6±1.0 vs 2.3±1.1, P<0.0001; Pain Assessment in Advanced Dementia, 6.9±1.6 vs 0.9±0.8, P<0.0001). Substantial improvements from T0 to T45 in daily functioning (mean Barthel index, 32.2±16.8 vs 53.7±23.9, P<0.0001) and neuropsychiatric symptoms (mean Neuropsychiatric Inventory, 25.5±27.3 vs 8.8±9.0, P<0.0001) were also reported. OXN-PR was well tolerated and did not worsen bowel function. Conclusion In this pilot study, OXN-PR was effective in improving pain and other symptoms associated with dementia, with a favorable safety and tolerability profile. Large-scale trials in people with dementia are needed to improve clinical guidance for the assessment and treatment of pain in

  17. A new therapeutic option for postoperative pain management with oxycodone HCI injection.

    PubMed

    Choi, Byung Moon

    2016-06-01

    Fentanyl is the most commonly used opioid analgesic in intravenous patient-controlled analgesia (IV PCA) in Korea. IV oxycodone was approved for postoperative IV PCA by the Ministry of Food and Drug Safety of Korea in 2013. The approved dosage regimen for postoperative pain relief with IV oxycodone is IV bolus loading of 2 mg followed by PCA composed of demand boluses of 1 mg and no background infusion with an oxycodone concentration of 1 mg/ml. However, a simulation study indicated that the minimum effective analgesic concentration (MEAC, as indicated by relief of pain by administering rescue analgesics) of oxycodone was reached most quickly with a higher loading dose of 0.1 mg/kg and IV PCA with background infusion. Oxycodone is a therapeutic option as an analgesic for postoperative pain management. It is necessary to reduce the analgesic dose of oxycodone in elderly patients because metabolic clearance decreases with age. PMID:27274364

  18. A new therapeutic option for postoperative pain management with oxycodone HCI injection

    PubMed Central

    2016-01-01

    Fentanyl is the most commonly used opioid analgesic in intravenous patient-controlled analgesia (IV PCA) in Korea. IV oxycodone was approved for postoperative IV PCA by the Ministry of Food and Drug Safety of Korea in 2013. The approved dosage regimen for postoperative pain relief with IV oxycodone is IV bolus loading of 2 mg followed by PCA composed of demand boluses of 1 mg and no background infusion with an oxycodone concentration of 1 mg/ml. However, a simulation study indicated that the minimum effective analgesic concentration (MEAC, as indicated by relief of pain by administering rescue analgesics) of oxycodone was reached most quickly with a higher loading dose of 0.1 mg/kg and IV PCA with background infusion. Oxycodone is a therapeutic option as an analgesic for postoperative pain management. It is necessary to reduce the analgesic dose of oxycodone in elderly patients because metabolic clearance decreases with age. PMID:27274364

  19. Efficacy and safety of combined prolonged-release oxycodone and naloxone in the management of moderate/severe chronic non-malignant pain: results of a prospectively designed pooled analysis of two randomised, double-blind clinical trials

    PubMed Central

    2010-01-01

    Background Two randomised 12-week, double-blind, parallel-group, multicenter studies comparing oxycodone PR/naloxone PR and oxycodone PR alone on symptoms of opioid-induced bowel dysfunction in patients with moderate/severe non-malignant pain have been conducted. Methods These studies were prospectively designed to be pooled and the primary outcome measure of the pooled data analysis was to demonstrate non-inferiority in 12-week analgesic efficacy of oxycodone PR/naloxone PR versus oxycodone PR alone. Patients with opioid-induced constipation were switched to oxycodone PR and then randomised to fixed doses of oxycodone PR/naloxone PR (n = 292) or oxycodone PR (n = 295) for 12 weeks (20-80 mg/day). Results No statistically significant differences in analgesic efficacy were observed for the two treatments (p = 0.3197; non-inferiority p < 0.0001; 95% CI -0.07, 0.23) and there was no statistically significant difference in frequency of analgesic rescue medication use. Improvements in Bowel Function Index score were observed for oxycodone PR/naloxone PR by Week 1 and at every subsequent time point (-15.1; p < 0.0001; 95% CI -17.3, -13.0). AE incidence was similar for both groups (61.0% and 57.3% of patients with oxycodone PR/naloxone PR and oxycodone PR alone, respectively). Conclusions Results of this pooled analysis confirm that oxycodone PR/naloxone PR provides effective analgesia and suggest that oxycodone PR/naloxone PR improves bowel function without compromising analgesic efficacy. Trial registration numbers ClinicalTrials.gov identifier: NCT00412100 and NCT00412152 PMID:20920236

  20. Pharmacokinetics and bioavailability of oxycodone and acetaminophen following single-dose administration of MNK-795, a dual-layer biphasic IR/ER combination formulation, under fed and fasted conditions

    PubMed Central

    Devarakonda, Krishna; Morton, Terri; Margulis, Rachel; Giuliani, Michael; Barrett, Thomas

    2014-01-01

    Background XARTEMIS™ XR (formerly MNK-795) is a combination oxycodone (OC) and acetaminophen (APAP) analgesic with both immediate-release and extended-release (ER) components (ER OC/APAP). The tablets are designed with gastric-retentive ER oral delivery technology that releases the ER component at a controlled rate in the upper gastrointestinal tract. Because consumption of food has demonstrated an impact on the pharmacokinetics (PK) of some marketed products using gastric-retentive ER oral delivery technology, a characterization of the effects of fed (high- and low-fat diets) versus fasted conditions on the PK of ER OC/APAP was performed. Methods This Phase I study used an open-label randomized single-dose three-period six-sequence crossover single-center design. Healthy adult participants (n=48) were randomized to receive two tablets of ER OC/APAP under three conditions: following a high-fat meal; following a low-fat meal; and fasted. Plasma concentration versus time data from predose throughout designated times up to 48 hours postdose was used to estimate the PK parameters of oxycodone and APAP. Results Thirty-one participants completed all three treatment periods. Both oxycodone and APAP were rapidly absorbed under fasted conditions. Total oxycodone and APAP exposures (area under the plasma drug concentration-time curve [AUC]) from ER OC/APAP were not significantly affected by food, and minimal changes to maximum observed plasma concentration for oxycodone and APAP were also noted. However, food marginally delayed the time to maximum observed plasma concentration of oxycodone and APAP. There was no indication that tolerability was affected by food. Conclusion The findings from this study suggest that ER OC/APAP can be administered with or without food. PMID:25170252

  1. The Adverse Events of Oxycodone in Cancer-Related Pain

    PubMed Central

    Ma, Hu; Liu, Yuan; Huang, Lang; Zeng, Xian-Tao; Jin, Su-Han; Yue, Guo-Jun; Tian, Xu; Zhou, Jian-Guo

    2016-01-01

    Abstract The adverse events (AEs) of oxycodone in cancer-related pain were controversial, so we conducted a meta-analysis to determine it. PubMed, Embase, CBM, CNKI, WanFang database, The Cochrane library, Web of Science, and the reference of included studies were searched to recognize pertinent studies. Relative risk (RR) with 95% confidence intervals (CIs) for all AEs were all extracted. The fixed-effects model was used to calculate pooled RRs and 95% CIs. Power calculation was performed using macro embedded in SAS software after all syntheses were completed. We identified 11 eligible trials involving 1211 patients: 604 patients included in oxycodone group and 607 patients involved in control group. Our quantitative analysis included 8 AEs, and the pooled analyses indicated that oxycodone compared with other opioids in cancer-related pain were not significantly decreased RRs of all AEs (dizziness RR = 0.94, 95% CI: 0.69–1.30, Z = 0.35, P = 0.72; nausea RR = 0.88, 95% CI: 0.72–1.07, Z = 1.26, P = 0.21; vomiting RR = 0.89, 95% CI: 0.70–1.15, Z = 0.9, P = 0.37; sleepiness RR = 0.86, 95% CI: 0.38–1.36, Z = 0.36, P = 0.72; constipation RR = 0.98, 95% CI: 0.81–1.19, Z = 0.21, P = 0.83; anorexia RR = 0.97, 95% CI = 0.58–1.62, Z = 0.11, P = 0.91; pruritus RR = 0.76, 95% CI: 0.44–1.30, Z = 1.01, P = 0.31; dysuria RR = 0.33, 95% CI: 0.07–1.62, Z = 1.36, P = 0.1)]. The subgroup analysis shown that Ox controlled-release (CR) had less sleepiness compared with MS-contin (Mc) CR (RR = 0.47, 95% CI: 0.25–0.90, P = 0.02). The power analysis suggests that all AEs have low statistical power. The present meta-analysis detected that no statistically significant difference were found among oxycodone and other opioids in all AEs, but Ox CR may had less sleepiness compared with Mc CR when subgroup analysis were conducted. PMID:27082588

  2. Postoperative oxycodone toxicity in a patient with chronic pain and end-stage renal disease.

    PubMed

    Tran, Bryant W; Kohan, Lynn R; Vorenkamp, Kevin E

    2015-02-15

    We present this case to review the metabolism of oxycodone and the effects of end-stage renal disease on the elimination of oxycodone and its metabolites. A 42-year-old female with end-stage renal disease who was dependent on hemodialysis presented for left hamstring posterior capsule release. She had been receiving methadone for 2 years for chronic leg pain. On postoperative day 1, the patient's medication was changed from IV hydromorphone to oral oxycodone to treat breakthrough pain. By the next day, the patient was unarousable with notable respiratory depression. She did not fully recover after urgent hemodialysis but did have full recovery after receiving an IV naloxone infusion for 22 hours. Further study of the safety of oxycodone in hemodialysis patients is warranted. PMID:25689360

  3. Oxycodone accumulation in a hemodialysis patient.

    PubMed

    Foral, Pamela A; Ineck, Joseph R; Nystrom, Kelly K

    2007-02-01

    Oxycodone and oxycodone-containing analgesics are often used for the relief of pain. In the presence of renal dysfunction, the half-life of oxycodone and metabolites can be prolonged. We describe the case of a 41-year-old chronic hemodialysis patient who received multiple doses of oxycodone/acetaminophen resulting in accumulation of the medication and consequent lethargy, hypotension and respiratory depression. These adverse effects were reversed with multiple bolus doses of naloxone, followed by a continuous infusion administered for 45 hours. Utilizing the Naranjo probability scale, the patient had a "probable" adverse drug reaction to the oxycodone. Oxycodone should be used with caution in patients with chronic renal failure. PMID:17330696

  4. Enhanced GABAergic synaptic transmission at VLPAG neurons and potent modulation by oxycodone in a bone cancer pain model

    PubMed Central

    Takasu, Keiko; Ogawa, Koichi; Nakamura, Atsushi; Kanbara, Tomoe; Ono, Hiroko; Tomii, Takako; Morioka, Yasuhide; Hasegawa, Minoru; Shibasaki, Masahiro; Mori, Tomohisa; Suzuki, Tsutomu; Sakaguchi, Gaku

    2015-01-01

    Background and Purpose We demonstrated previously that oxycodone has potent antinociceptive effects at supraspinal sites. In this study, we investigated changes in neuronal function and antinociceptive mechanisms of oxycodone at ventrolateral periaqueductal gray (VLPAG) neurons, which are a major site of opioid action, in a femur bone cancer (FBC) model with bone cancer-related pain. Experimental Approach We characterized the supraspinal antinociceptive profiles of oxycodone and morphine on mechanical hypersensitivity in the FBC model. Based on the disinhibition mechanism underlying supraspinal opioid antinociception, the effects of oxycodone and morphine on GABAA receptor-mediated inhibitory postsynaptic currents (IPSCs) in VLPAG neurons were evaluated in slices from the FBC model. Key Results The supraspinal antinociceptive effects of oxycodone, but not morphine, were abolished by blocking G protein-gated inwardly rectifying potassium1 (Kir3.1) channels. In slices from the FBC model, GABAergic synaptic transmission at VLPAG neurons was enhanced, as indicated by a leftward shift of the input–output relationship curve of evoked IPSCs, the increased paired-pulse facilitation and the enhancement of miniature IPSC frequency. Following treatment with oxycodone and morphine, IPSCs were reduced in the FBC model, and the inhibition of presynaptic GABA release by oxycodone, but not morphine was enhanced and dependent on Kir3.1 channels. Conclusion and Implications Our results demonstrate that Kir3.1 channels are important for supraspinal antinociception and presynaptic GABA release inhibition by oxycodone in the FBC model. Enhanced GABAergic synaptic transmission at VLPAG neurons in the FBC model is an important site of supraspinal antinociception by oxycodone via Kir3.1 channel activation. PMID:25521524

  5. Controlled Release Applications of Organometals.

    ERIC Educational Resources Information Center

    Thayer, John S.

    1981-01-01

    Reviews two classes of controlled release organometals: (1) distributional, to distribute bioactive materials to control a certain target organism; and (2) protective, to protect surface or interior of some structure from attach by organisms. Specific examples are given including a discussion of controlled release for schistosomiasis. (SK)

  6. CYP2D6 Genotype Dependent Oxycodone Metabolism in Postoperative Patients

    PubMed Central

    Stamer, Ulrike M.; Zhang, Lan; Book, Malte; Lehmann, Lutz E.; Stuber, Frank; Musshoff, Frank

    2013-01-01

    Background The impact of polymorphic cytochrome P450 CYP2D6 enzyme on oxycodone's metabolism and clinical efficacy is currently being discussed. However, there are only spare data from postoperative settings. The hypothesis of this study is that genotype dependent CYP2D6 activity influences plasma concentrations of oxycodone and its metabolites and impacts analgesic consumption. Methods Patients received oxycodone 0.05 mg/kg before emerging from anesthesia and patient-controlled analgesia (PCA) for the subsequent 48 postoperative hours. Blood samples were drawn at 30, 90 and 180 minutes after the initial oxycodone dose. Plasma concentrations of oxycodone and its metabolites oxymorphone, noroxycodone and noroxymorphone were analyzed by liquid chromatography-mass spectrometry with electrospray ionization. CYP2D6 genotyping was performed and 121 patients were allocated to the following genotype groups: PM (poor metabolizer: no functionally active CYP2D6 allele), HZ/IM (heterozygous subjects, intermediate metabolizers with decreased CYP2D6 activity), EM (extensive metabolizers, normal CYP2D6 activity) and UM (ultrarapid metabolizers, increased CYP2D6 activity). Primary endpoint was the genotype dependent metabolite ratio of plasma concentrations oxymorphone/oxycodone. Secondary endpoint was the genotype dependent analgesic consumption with calculation of equianalgesic doses compared to the standard non-CYP dependent opioid piritramide. Results Metabolism differed between CYP2D6 genotypes. Mean (95%-CI) oxymophone/oxycodone ratios were 0.10 (0.02/0.19), 0.13 (0.11/0.16), 0.18 (0.16/0.20) and 0.28 (0.07/0.49) in PM, HZ/IM, EM and UM, respectively (p = 0.005). Oxycodone consumption up to the 12th hour was highest in PM (p = 0.005), resulting in lowest equianalgesic doses of piritramide versus oxycodone for PM (1.6 (1.4/1.8); EM and UM 2.2 (2.1/2.3); p<0.001). Pain scores did not differ between genotypes. Conclusions In this postoperative setting, the number of

  7. Efficacy and tolerability of low-dose oral prolonged-release oxycodone/naloxone for chronic nononcological pain in older patients

    PubMed Central

    Guerriero, Fabio; Sgarlata, Carmelo; Marcassa, Claudio; Ricevuti, Giovanni; Rollone, Marco

    2015-01-01

    Purpose Chronic pain is highly prevalent in older adults. Increasing evidence indicates strong opioids as a valid option for chronic pain management in geriatrics. The aim of this study was to evaluate efficacy and safety of low-dose oral prolonged-release oxycodone–naloxone (OXN-PR) in patients aged ≥70 years. Methods This open-label prospective study assessed older patients naïve to strong opioids presenting with moderate-to-severe chronic pain. Patients were prescribed OXN-PR at an initial dose of 10/5 mg/day for 28 days. In case of insufficient analgesia, the initial daily dose could be increased gradually. The primary efficacy measure was change in pain intensity from baseline, assessed by a ten-point Numeric Rating Scale (NRS) at day 28 (T28). Changes in cognitive state, daily functioning, quality of life, constipation, and other adverse events were assessed. Results Of 53 patients enrolled (mean 81.7±6.2 years [range 70–92 years]), 52 (98.1%) completed the 28-day observation. At T28, the primary end point (≥30% reduction in mean pain from baseline in the absence of bowel function deterioration) was achieved in 38 patients (71.7%). OXN-PR significantly relieved pain (NRS score –3.26; P<0.0001), as well as daily need for rescue paracetamol (from 86.8% at baseline to 40.4% at T28; P<0.001), and reduced impact of pain on daily activities (Brief Pain Inventory Short Form from 6.2±1.5 to 3.4±2.1; P<0.0001). OXN-PR was also associated with significant improvement in daily functioning (Barthel Index from 53.3±14.1 to 61.3±14.3; P<0.01). No changes were observed in cognitive status and bowel function. OXN-PR was well tolerated; only one patient (1.9%) prematurely withdrew from treatment, due to drowsiness. Conclusion Findings from this open-label prospective study suggest that low-dose OXN-PR may be effective and well tolerated for treatment of moderate-to-severe chronic pain in older patients. Besides its effectiveness, these data indicate that low

  8. Switching to low-dose oral prolonged-release oxycodone/naloxone from WHO-Step I drugs in elderly patients with chronic pain at high risk of early opioid discontinuation

    PubMed Central

    Lazzari, Marzia; Marcassa, Claudio; Natoli, Silvia; Carpenedo, Roberta; Caldarulo, Clarissa; Silvi, Maria B; Dauri, Mario

    2016-01-01

    Purpose Chronic pain has a high prevalence in the aging population. Strong opioids also should be considered in older people for the treatment of moderate to severe pain or for pain that impairs functioning and the quality of life. This study aimed to assess the efficacy and safety of the direct switch to low-dose strong opioids (World Health Organization-Step III drugs) in elderly, opioid-naive patients. Patients and methods This was a single-center, retrospective, observational study in opioid-naive patients aged ≥75 years, with moderate to severe chronic pain (>6-month duration) and constipation, who initiated treatment with prolonged-release oxycodone/naloxone (OXN-PR). Patients were re-evaluated after 15, 30, and 60 days (T60, final observation). Response to treatment was defined as an improvement in pain of ≥30% after 30 days of therapy without worsening of constipation. Results One-hundred and eighty-six patients (mean ± SD age 80.7±4.7 years; 64.5% women) with severe chronic pain (mean average pain intensity 7.1±1.0 on the 11-point numerical rating scale) and constipation (mean Bowel Function Index 64.1±24.4; 89.2% of patients on laxatives) were initiated treatment with OXN-PR (mean daily dose 11.3±3.5 mg). OXN-PR reduced pain intensity rapidly and was well tolerated; 63.4% of patients responded to treatment with OXN-PR. At T60 (mean daily OXN-PR dose, 21.5±9.7 mg), the pain intensity was reduced by 66.7%. In addition, bowel function improved (mean decrease of Bowel Function Index from baseline to T60, −28.2, P<0.0001) and the use of laxatives decreased. Already after 15 days and throughout treatment, ~70% of patients perceived their status as much/extremely improved. Only 1.6% of patients discontinued treatment due to adverse events. Conclusion Low-dose OXN-PR in elderly patients naive to opioids proved to be an effective option for the treatment of moderate to severe chronic pain. Large-scale trials are needed to improve clinical guidance in

  9. Optogenetic control of ATP release

    NASA Astrophysics Data System (ADS)

    Lewis, Matthew A.; Joshi, Bipin; Gu, Ling; Feranchak, Andrew; Mohanty, Samarendra K.

    2013-03-01

    Controlled release of ATP can be used for understanding extracellular purinergic signaling. While coarse mechanical forces and hypotonic stimulation have been utilized in the past to initiate ATP release from cells, these methods are neither spatially accurate nor temporally precise. Further, these methods cannot be utilized in a highly effective cell-specific manner. To mitigate the uncertainties regarding cellular-specificity and spatio-temporal release of ATP, we herein demonstrate use of optogenetics for ATP release. ATP release in response to optogenetic stimulation was monitored by Luciferin-Luciferase assay (North American firefly, photinus pyralis) using luminometer as well as mesoscopic bioluminescence imaging. Our result demonstrates repetitive release of ATP subsequent to optogenetic stimulation. It is thus feasible that purinergic signaling can be directly detected via imaging if the stimulus can be confined to single cell or in a spatially-defined group of cells. This study opens up new avenue to interrogate the mechanisms of purinergic signaling.

  10. A tale of 2 ADFs: differences in the effectiveness of abuse-deterrent formulations of oxymorphone and oxycodone extended-release drugs.

    PubMed

    Cicero, Theodore J; Ellis, Matthew S; Kasper, Zachary A

    2016-06-01

    The introduction of extended-release opioid analgesics helped initiate an epidemic of prescription opioid abuse in the United States. To make access to the drug by crushing or dissolution more difficult, abuse-deterrent formulations (ADFs) of OxyContin (Purdue Pharma, Stamford, CT) and Opana ER (Endo Pharmaceuticals Inc., Malvern, PA), which use the same foundation technology (Intac, Grunenthal, Aachen, Germany), were introduced in 2010 and 2012, respectively. To examine their relative effectiveness, we used a structured survey of 12,124 individuals entering treatment for opioid use disorder followed by a more focused online survey with a subset of these patients (N = 129) using both structured and open-ended questions. Data showed that the OxyContin ADF was highly effective in reducing nonoral abuse (91.4% before the ADF, 47.9% afterwards), particularly with insufflation (78%-28.8%) and intravenous injection of the active drug (42.7%-21.4%). However, although the Opana ER ADF was effective in reducing insufflation (80%-37.1%), injection (60.0%-51.4%), and overall nonoral abuse (94.3%-77.1%), it showed no significant decrease over time. Bearing in mind that the Opana ER sample was smaller in size than that for OxyContin, our results nonetheless suggest disparate outcomes resulting from the introduction of the ADFs, which could indicate that an ADF's effectiveness may be drug-specific. Given the public health impact of prescription opioids and the considerable effort being expended to develop ADFs as a partial solution to the problem, our preliminary studies suggest that each ADF must be evaluated on its own merits even if the same proprietary technology is used. PMID:27186712

  11. Controlled Release from Recombinant Polymers

    PubMed Central

    Price, Robert; Poursaid, Azadeh; Ghandehari, Hamidreza

    2014-01-01

    Recombinant polymers provide a high degree of molecular definition for correlating structure with function in controlled release. The wide array of amino acids available as building blocks for these materials lend many advantages including biorecognition, biodegradability, potential biocompatibility, and control over mechanical properties among other attributes. Genetic engineering and DNA manipulation techniques enable the optimization of structure for precise control over spatial and temporal release. Unlike the majority of chemical synthetic strategies used, recombinant DNA technology has allowed for the production of monodisperse polymers with specifically defined sequences. Several classes of recombinant polymers have been used for controlled drug delivery. These include, but are not limited to, elastin-like, silk-like, and silk-elastinlike proteins, as well as emerging cationic polymers for gene delivery. In this article, progress and prospects of recombinant polymers used in controlled release will be reviewed. PMID:24956486

  12. Controlled release liquid dosage formulation

    DOEpatents

    Benton, Ben F.; Gardner, David L.

    1989-01-01

    A liquid dual coated dosage formulation sustained release pharmaceutic having substantial shelf life prior to ingestion is disclosed. A dual coating is applied over controlled release cores to form dosage forms and the coatings comprise fats melting at less than approximately 101.degree. F. overcoated with cellulose acetate phthalate or zein. The dual coated dosage forms are dispersed in a sugar based acidic liquid carrier such as high fructose corn syrup and display a shelf life of up to approximately at least 45 days while still retaining their release profiles following ingestion. Cellulose acetate phthalate coated dosage form cores can in addition be dispersed in aqueous liquids of pH <5.

  13. Effects of cold pressor pain on the abuse liability of intranasal oxycodone in male and female prescription opioid abusers

    PubMed Central

    Lofwall, Michelle R.; Nuzzo, Paul A.; Walsh, Sharon L.

    2012-01-01

    Background Approximately 1.9 million persons in the U.S. have prescription opioid use disorders often with concomitant bodily pain, but systematic data on the impact of pain on abuse liability of opioids is lacking. The purpose of this study was to determine whether pain alters the intranasal abuse liability of oxycodone, a commonly prescribed and abused analgesic, in males and females. Methods Sporadic prescription opioid abusers (10 females, 10 males) participated in this mixed (between and within-subject), randomized inpatient study. Experimental sessions (n=6) tested intranasal placebo, oxycodone 15 or 30 mg/70 kg during cold pressor testing (CPT) and a warm water control. Observer- and subject-rated drug effect measures, analgesia, physiologic and cognitive effects were assessed. Results The CPT significantly increased blood pressure, heart rate, pain, stress, and “opiate desire” compared to the no-pain control but did not alter opioid liking, high or street value. Intranasal oxycodone produced effects within 10 minutes, significantly decreasing pain and significantly increasing subjective measures of abuse liability (e.g., high). Females had higher ratings of street value, high, and liking for one or both active doses. Conclusions The CPT was a reliably painful and stressful stimulus that did not diminish the abuse liability of intranasal Oxycodone®. Females were more sensitive to oxycodone on several abuse liability measures that warrant further follow-up. Snorting oxycodone rapidly produced psychoactive effects indicative of substantial abuse liability. PMID:22209386

  14. Oxycodone/Naloxone: role in chronic pain management, opioid-induced constipation, and abuse deterrence.

    PubMed

    DePriest, Anne Z; Miller, Katie

    2014-06-01

    The use of opioids in the treatment of chronic pain is widespread; the prevalence of specific opioids varies from country to country and depends on product availability, national formulary systems, and provider preferences. Patients often receive opioids for legitimate treatment of pain conditions, but on the opposite side of the spectrum, nonmedical use of opioids is a significant public health concern. Opioids are associated with several side effects, and constipation is the most commonly reported and persistent symptom. Unlike some adverse effects associated with opioid use, tolerance does not develop to constipation. Opioid-induced constipation (OIC) is the most prevalent patient complaint associated with opioid use and has been associated with declines in various quality of life measures. OIC can be extremely difficult for patients to tolerate and may prompt patients to decrease or discontinue opioid treatment. Current management strategies for OIC are often insufficient. A prolonged-release formulation of oxycodone/naloxone (OXN) has been investigated for the treatment of nonmalignant and cancer pain and mitigation of OIC, and evidence is largely favorable. Studies have demonstrated the capability of OXN to alleviate OIC while maintaining pain control comparable to oxycodone-only regimens. There is insufficient evidence for OXN efficacy for patients with mild OIC or patients maintained on high doses of opioids, and use in these populations is controversial. The reduction of costs associated with OIC may provide overall cost effectiveness with OXN. Additionally, the presence of naloxone may deter abuse/misuse by those seeking to misuse the formulation by modes of administration other than oral ingestion. Most studies to date have occurred in European countries, and phase 3 trials continue in the United States. This review will include current therapeutic options for pain and constipation, unique characteristics of OXN, evidence related to use of OXN and its

  15. Comparison of relative oxycodone consumption in surgical pleth index-guided analgesia versus conventional analgesia during sevoflurane anesthesia

    PubMed Central

    Won, Young Ju; Lim, Byung Gun; Lee, So Hyun; Park, Sangwoo; Kim, Heezoo; Lee, Il Ok; Kong, Myoung Hoon

    2016-01-01

    Abstract Background: The surgical pleth index (SPI) is proposed for titration of analgesic drugs during general anesthesia. Several reports have investigated the effect of SPI on the consumption of opioids including remifentanil, fentanyl, and sufentanil during anesthesia, but there are no reports about oxycodone. We aimed to investigate intravenous oxycodone consumption between SPI-guided analgesia and conventional analgesia practices during sevoflurane anesthesia in patients undergoing thyroidectomy. Methods: Forty-five patients undergoing elective thyroidectomy were randomly assigned to an SPI group (SPI-guided analgesia group, n = 23) or a control group (conventional analgesia group, n = 22). Anesthesia was maintained with sevoflurane to achieve bispectral index values between 40 and 60. In the SPI group, oxycodone 1 mg was administered intravenously at SPI values over 50; in the control group, oxycodone 1 mg was administered intravenously at the occurrence of tachycardia or hypertension event. Intraoperative oxycodone consumption and extubation time were recorded. The number of hemodynamic and somatic movement events was recorded, as were postoperative pain and recovery scores. Results: Patients’ characteristics were comparable between the groups. Intraoperative oxycodone consumption in the SPI group was significantly lower than the control group (3.5 ± 2.4 vs 5.1 ± 2.4 mg; P = 0.012). Extubation time was significantly shorter in the SPI group (10.6 ± 3.5 vs 13.4 ± 4.6 min; P = 0.026). Hemodynamic and somatic movement events during anesthesia were comparable between the groups, as were numeric rating scales for pain and modified Aldrete scores at postanesthesia care unit. Conclusions: SPI-guided analgesia reduces intravenous oxycodone consumption and extubation time compared with conventional analgesia based on clinical parameters during sevoflurane anesthesia in patients undergoing thyroidectomy. PMID:27583920

  16. An update on oxycodone: lessons for death investigators in Australia.

    PubMed

    Pilgrim, Jennifer L; Yafistham, Sabrina Putrianita; Gaya, Sanjeev; Saar, Eva; Drummer, Olaf H

    2015-03-01

    Oxycodone is one of the most abused prescription drugs. Iatrogenic factors that lead to oxycodone-related death, such as mis-prescribing, present an opportunity for death prevention if identified early. This study investigated deaths involving oxycodone in Australia to explore potentially inappropriate prescribing and the coroner's investigation. The National Coronial Information System identified cases from 2001 to 2011 where oxycodone was detected by toxicological analysis. There were 806 oxycodone-related deaths, with a significant increase in the 11-year period, from 21 deaths in 2001, up almost sevenfold in 2011 (139 deaths). Most deaths were caused by combined drug toxicity (63.4%) or oxycodone toxicity alone (11.8%). Most individuals were male (59.1%), aged 35-44 years (26.7%), who died unintentionally (56.4%), with mental illness (52.1%) and/or a history of acute or chronic pain (46.2%). 312 cases (39%) described a legitimate prescription for oxycodone, of which most involved non-cancer related chronic pain. About three quarters of the indications were deemed appropriate. There were at least 43 different indications treated with oxycodone that were inappropriate. The majority of oxycodone-related cases involved minor to no description of the drugs involved (n = 600; 74.4%). A moderate description of oxycodone involvement was given in 162 cases (20.1%), while only 44 cases (5.5%) involved a thorough examination and recommendations from the coroners on oxycodone and other drugs involved in death. This study emphasized the need for medical practitioners to exercise caution when prescribing oxycodone and for coroners to provide more consistent and detailed information regarding drug use, in order to identify and implement preventive strategies. PMID:25403552

  17. Prenatal oxycodone exposure impairs spatial learning and/or memory in rats.

    PubMed

    Davis, Chris P; Franklin, La'tonya M; Johnson, Gabriel S; Schrott, Lisa M

    2010-09-01

    Recent changes in demographic patterns of drug use have resulted in the increased non-medical use of prescription opiates. These users are younger and more likely to be female, which has the potential for increasing rates of in utero exposure. Therefore, we developed a rat model that simulates a prescription opiate-dependent woman who becomes pregnant. Adult female Sprague-Dawley rats were treated for 30 days via oral gavage with ascending doses of oxycodone HCl up to a final dose of 15mg/kg/day, which was maintained during breeding and gestation. Controls were treated with water. The adult male offspring of these treated dams were tested on the radial arm maze, the Morris water maze (with a short and a long intertrial interval), and a spatial T-maze. Prenatal oxycodone exposure led to a deficit in the radial arm maze characterized by a greater number of reference memory errors, especially in the beginning of testing. In contrast, in the T-maze, prenatal oxycodone-exposed rats learned the task as well as well as the prenatal water controls. However, they had a modest deficit in retention of the task when assessed 5 days after acquisition training ended. For the Morris water maze, the intertrial interval affected the pattern of learning. While there was no deficit when the training had a short intertrial interval, when there was a long intertrial interval, prenatal oxycodone-exposed rats had poorer acquisition. The spatial learning deficit was characterized by and increased latency to find and a greater distance traveled to the platform in the prenatal oxycodone-exposed rats. These data were corroborated by analysis of the behavioral search strategy, which showed a decreased use of spatial strategies and an increase in non-spatial strategies, especially wall-hugging, in prenatal oxycodone-exposed rats as compared to prenatal water control rats on day 2 of acquisition. These results indicate that prenatal oxycodone exposure consistently impairs learning and memory in

  18. 78 FR 23273 - Determination That the OXYCONTIN (Oxycodone Hydrochloride) Drug Products Covered by New Drug...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-18

    ...The Food and Drug Administration (FDA) has determined that OXYCONTIN (oxycodone hydrochloride) extended-release tablets (10 milligrams (mg), 15 mg, 20 mg, 30 mg, 40 mg, 60 mg, 80 mg, and 160 mg) approved under new drug application (NDA) 20-553 were withdrawn from sale for reasons of safety or effectiveness. The Agency will not accept or approve abbreviated new drug applications (ANDAs) for......

  19. Controlled Drug Release from Pharmaceutical Nanocarriers

    PubMed Central

    Lee, Jinhyun Hannah; Yeo, Yoon

    2014-01-01

    Nanocarriers providing spatiotemporal control of drug release contribute to reducing toxicity and improving therapeutic efficacy of a drug. On the other hand, nanocarriers face unique challenges in controlling drug release kinetics, due to the large surface area per volume ratio and the short diffusion distance. To develop nanocarriers with desirable release kinetics for target applications, it is important to understand the mechanisms by which a carrier retains and releases a drug, the effects of composition and morphology of the carrier on the drug release kinetics, and current techniques for preparation and modification of nanocarriers. This review provides an overview of drug release mechanisms and various nanocarriers with a specific emphasis on approaches to control the drug release kinetics. PMID:25684779

  20. Quality of life under oxycodone/naloxone, oxycodone, or morphine treatment for chronic low back pain in routine clinical practice

    PubMed Central

    Ueberall, Michael A; Eberhardt, Alice; Mueller-Schwefe, Gerhard HH

    2016-01-01

    Objective To compare the quality of life of patients with moderate-to-severe chronic low back pain under treatment with the WHO-step III opioids oxycodone/naloxone, oxycodone, or morphine in routine clinical practice. Study design Prospective, 12-week, randomized, open-label, blinded end-point study in 88 medical centers in Germany. Patients and methods A total of 901 patients requiring around-the-clock pain treatment with a WHO-step III opioid were randomized to either morphine, oxycodone, or oxycodone/naloxone (1:1:1). Changes from baseline to week 12 in quality of life were assessed using different validated tools (EuroQoL-5 Dimensions [EQ-5D], Short Form 12 [SF-12], quality of life impairment by pain inventory [QLIP]). Results EQ-5D weighted index scores significantly improved over the 12-week treatment period under all three opioids (P<0.001) with significantly greater improvements under oxycodone/naloxone (65.2% vs 49.6% for oxycodone and 48.2% for morphine, P<0.001). The proportion of patients without EQ-5D complaints was also significantly higher under oxycodone/naloxone (P<0.001). Although quality of life ratings with the QLIP inventory showed significant improvements in all the three treatment arms, improvements were significantly higher under oxycodone/naloxone than under oxycodone and morphine (P<0.001): 90.7% of all oxycodone/naloxone patients achieved ≥30% improvements in quality of life, 72.8% had ≥50%, and 33.2% ≥70% improvements. Similarly, both physical and mental SF-12 component scores showed significantly greater improvements under oxycodone/naloxone with both scores close to the German population norm after 12 weeks. Conclusion Treatment with morphine, oxycodone, or oxycodone/naloxone under routine daily practice conditions significantly improved state of health and quality of life of patients with moderate-to-severe low back pain over a 12-week treatment period. Comparison between the treatment groups showed significantly greater

  1. Comparison of a drug versus money and drug versus drug self-administration choice procedure with oxycodone and morphine in opioid addicts.

    PubMed

    Comer, Sandra D; Metz, Verena E; Cooper, Ziva D; Kowalczyk, William J; Jones, Jermaine D; Sullivan, Maria A; Manubay, Jeanne M; Vosburg, Suzanne K; Smith, Mary E; Peyser, Deena; Saccone, Phillip A

    2013-09-01

    This double-blind, placebo-controlled study investigated the effects of oral morphine (0, 45, 135 mg/70 kg) and oral oxycodone (0, 15, 45 mg/70 kg) on buprenorphine-maintained opioid addicts. As a 3: 1 morphine : oxycodone oral dose ratio yielded equivalent subjective and physiological effects in nondependent individuals, this ratio was used in the present study. Two self-administration laboratory procedures - that is, a drug versus money and a drug versus drug procedure - were assessed. Study participants (N=12) lived in the hospital and were maintained on 4 mg/day sublingual buprenorphine. When participants chose between drug and money, money was preferred over all drug doses; only high-dose oxycodone was self-administered more than placebo. When participants chose between drug and drug, both drugs were chosen more than placebo, high doses of each drug were chosen over low doses, and high-dose oxycodone was preferred over high-dose morphine. The subjective, performance-impairing, and miotic effects of high-dose oxycodone were generally greater than those of high-dose morphine. The study demonstrated that a 3: 1 oral dose ratio of morphine : oxycodone was not equipotent in buprenorphine-dependent individuals. Both self-administration procedures were effective for assessing the relative reinforcing effects of drugs; preference for one procedure should be driven by the specific research question of interest. PMID:23839029

  2. Comparison of a drug versus money and drug versus drug self-administration choice procedure with oxycodone and morphine in opioid addicts

    PubMed Central

    Comer, Sandra D; Metz, Verena E; Cooper, Ziva D; Kowalczyk, William J; Jones, Jermaine D; Sullivan, Maria A; Manubay, Jeanne M; Vosburg, Suzanne K; Smith, Mary E; Peyser, Deena; Saccone, Phillip A

    2014-01-01

    This double-blind, placebo-controlled study investigated effects of oral morphine (0, 45, 135 mg/70kg) and oral oxycodone (0, 15, 45 mg/70kg) in buprenorphine-maintained opioid addicts. Since a 3:1 morphine:oxycodone dose ratio had yielded equivalent subjective and physiological effects in non-dependent individuals, this ratio was used in the present study. Two self-administration laboratory procedures, i.e. a drug vs. money and a drug vs. drug procedure, were assessed. Study participants (N=12) lived in the hospital and were maintained on 4 mg/day sublingual buprenorphine. When participants chose between drug and money, money was preferred over all drug doses; only high-dose oxycodone was self-administered more than placebo. When participants chose between drug and drug, both drugs were chosen more than placebo, high doses of each drug were chosen over low doses, and high-dose oxycodone was preferred over high-dose morphine. The subjective, performance-impairing, and miotic effects of high-dose oxycodone were generally greater compared to high-dose morphine. The study demonstrated that a 3:1 dose ratio of morphine:oxycodone was not equipotent in buprenorphine-dependent subjects. Both self-administration procedures were effective for assessing the relative reinforcing effects of drugs; preference for one procedure should be driven by the specific research question of interest. PMID:23839029

  3. Birth control - slow release methods

    MedlinePlus

    Contraception - hormonal methods; Progestin implants; Progestin injections; Skin patch; Vaginal ring ... might want to consider a different birth control method. SKIN PATCH The skin patch is placed on ...

  4. Evaluation of ongoing oxycodone abuse among methadone-maintained patients.

    PubMed

    Dunn, Kelly E; Sigmon, Stacey C; McGee, Mark R; Heil, Sarah H; Higgins, Stephen T

    2008-12-01

    Prevalence of prescription opioid abuse has increased dramatically in recent years in the United States generally, and a similar pattern of increasing prescription opioid use has also been noted among patients seeking treatment for opioid dependence. This study presents results from an internal quality assurance project conducted by an outpatient methadone maintenance (MM) treatment clinic which sought to examine the extent of ongoing oxycodone abuse among patients that might be going undetected with current urinalysis-testing methods. One hundred five MM patients provided 437 urine samples over a 6-week period. Samples were analyzed using the clinic's usual enzyme multiplied immunoassay test (EMIT) opiate assay (300 ng/ml opiate cutpoint) and a supplemental oxycodone test strip (100 ng/ml oxycodone cutpoint). The EMIT assay identified only 6% (20/437) of samples as positive for oxycodone, whereas the oxycodone test strip indicated that 19% (83/437) tested positive for recent oxycodone use. Inspection of patient characteristics revealed that oxycodone users were more likely to report a prescription opioid as their primary drug at intake, be in MM treatment for a significantly shorter duration, and provide significantly more opioid- and cocaine-positive urine samples. Overall, these data illustrate the potential importance of monitoring for ongoing oxycodone use in MM clinics. Although future efforts should examine this question using more rigorous experimental methods, findings from this initial project have implications for clinical issues such as evaluating patient stability in treatment, making medication-dosing decisions, and determining patient eligibility for methadone take-home privileges. PMID:18295434

  5. Evaluation of Ongoing Oxycodone Abuse among Methadone-Maintained Patients

    PubMed Central

    Dunn, Kelly E.; Sigmon, Stacey C.; McGee, Mark R.; Heil, Sarah H; Higgins, Stephen T.

    2008-01-01

    Prevalence of prescription opioid abuse has increased dramatically in recent years in the United States generally, and a similar pattern of increasing prescription opioid use has also been noted among patients seeking treatment for opioid dependence. The current study presents results from an internal quality-assurance project conducted by an outpatient methadone-maintenance (MM) treatment clinic which sought to examine the extent of ongoing oxycodone abuse among patients that might be going undetected with current urinalysis testing methods. One-hundred and five MM patients provided 437 urine samples over a 6-week period. Samples were analyzed using the clinic’s usual enzyme multiplied immunoassay test (EMIT) opiate assay (300 ng/ml opiate cutpoint) and a supplemental oxycodone test strip (100 ng/ml oxycodone cutpoint). The EMIT assay identified only 6% (20/437) of samples as positive for oxycodone, while the oxycodone test strip indicated that 19% (83/437) tested positive for recent oxycodone use. Inspection of patient characteristics revealed that oxycodone users were more likely to report a prescription opioid as their primary drug at intake, be in MM treatment for a significantly shorter duration and provide significantly more opioid- and cocaine-positive urine samples. Overall, these data illustrate the potential importance of monitoring for ongoing oxycodone use in MM clinics. While future efforts should examine this question using more rigorous experimental methods, findings from this initial project have implications for clinical issues such as evaluating patient stability in treatment, making medication dosing decisions, and determining patient eligibility for methadone take-home privileges. PMID:18295434

  6. G protein-gated inwardly rectifying potassium (KIR3) channels play a primary role in the antinociceptive effect of oxycodone, but not morphine, at supraspinal sites

    PubMed Central

    Nakamura, Atsushi; Fujita, Masahide; Ono, Hiroko; Hongo, Yoshie; Kanbara, Tomoe; Ogawa, Koichi; Morioka, Yasuhide; Nishiyori, Atsushi; Shibasaki, Masahiro; Mori, Tomohisa; Suzuki, Tsutomu; Sakaguchi, Gaku; Kato, Akira; Hasegawa, Minoru

    2014-01-01

    BACKGROUND AND PURPOSE Oxycodone and morphine are μ-opioid receptor agonists prescribed to control moderate-to-severe pain. Previous studies suggested that these opioids exhibit different analgesic profiles. We hypothesized that distinct mechanisms mediate the differential effects of these two opioids and investigated the role of G protein-gated inwardly rectifying potassium (KIR3 also known as GIRK) channels in their antinociceptive effects. EXPERIMENTAL APPROACH Opioid-induced antinociceptive effects were assessed in mice, using the tail-flick test, by i.c.v. and intrathecal (i.t.) administration of morphine and oxycodone, alone and following inhibition of KIR3.1 channels with tertiapin-Q (30 pmol per mouse, i.c.v. and i.t.) and KIR3.1-specific siRNA. The antinociceptive effects of oxycodone and morphine were also examined after tertiapin-Q administration in the mouse femur bone cancer and neuropathic pain models. KEY RESULTS The antinociceptive effects of oxycodone, after both i.c.v. and i.t. administrations, were markedly attenuated by KIR3.1 channel inhibition. In contrast, the antinociceptive effects of i.c.v. morphine were unaffected, whereas those induced by i.t. morphine were attenuated, by KIR3.1 channel inhibition. In the two chronic pain models, the antinociceptive effects of s.c. oxycodone, but not morphine, were inhibited by supraspinal administration of tertiapin-Q. CONCLUSION AND IMPLICATIONS These results demonstrate that KIR3.1 channels play a primary role in the antinociceptive effects of oxycodone, but not those of morphine, at supraspinal sites and suggest that supraspinal KIR3.1 channels are responsible for the unique analgesic profile of oxycodone. PMID:24117458

  7. Genetic polymorphisms and drug interactions modulating CYP2D6 and CYP3A activities have a major effect on oxycodone analgesic efficacy and safety

    PubMed Central

    Samer, CF; Daali, Y; Wagner, M; Hopfgartner, G; Eap, CB; Rebsamen, MC; Rossier, MF; Hochstrasser, D; Dayer, P; Desmeules, JA

    2010-01-01

    Background and purpose: The major drug-metabolizing enzymes for the oxidation of oxycodone are CYP2D6 and CYP3A. A high interindividual variability in the activity of these enzymes because of genetic polymorphisms and/or drug–drug interactions is well established. The possible role of an active metabolite in the pharmacodynamics of oxycodone has been questioned and the importance of CYP3A-mediated effects on the pharmacokinetics and pharmacodynamics of oxycodone has been poorly explored. Experimental approach: We conducted a randomized crossover (five arms) double-blind placebo-controlled study in 10 healthy volunteers genotyped for CYP2D6. Oral oxycodone (0.2 mg·kg−1) was given alone or after inhibition of CYP2D6 (with quinidine) and/or of CYP3A (with ketoconazole). Experimental pain (cold pressor test, electrical stimulation, thermode), pupil size, psychomotor effects and toxicity were assessed. Key results: CYP2D6 activity was correlated with oxycodone experimental pain assessment. CYP2D6 ultra-rapid metabolizers experienced increased pharmacodynamic effects, whereas cold pressor test and pupil size were unchanged in CYP2D6 poor metabolizers, relative to extensive metabolizers. CYP2D6 blockade reduced subjective pain threshold (SPT) for oxycodone by 30% and the response was similar to placebo. CYP3A4 blockade had a major effect on all pharmacodynamic assessments and SPT increased by 15%. Oxymorphone Cmax was correlated with SPT assessment (ρS= 0.7) and the only independent positive predictor of SPT. Side-effects were observed after CYP3A4 blockade and/or in CYP2D6 ultra-rapid metabolizers. Conclusions and implications: The modulation of CYP2D6 and CYP3A activities had clear effects on oxycodone pharmacodynamics and these effects were dependent on CYP2D6 genetic polymorphism. PMID:20590588

  8. Controlled drug release from hydrogel nanoparticle networks.

    PubMed

    Huang, Gang; Gao, Jun; Hu, Zhibing; St John, John V; Ponder, Bill C; Moro, Dan

    2004-02-10

    Monodisperse nanoparticles of poly-N-isopropylacrylamide-co-allylamine (PNIPAM-co-allylamine) and PNIPAM-co-acrylic acid (PNIPAM-co-AA) were synthesized. The close-packed PNIPAM-co-allylamine and PNIPAM-co-AA nanoparticles were converted to three-dimensional gel networks by covalently crosslinking neighboring particles at room temperature and neutral pH using glutaric dialdehyde and adipic acid dihydrazide, respectively. Controlled release studies were conducted using dextran markers of various molecular weights as model macromolecular drugs. Release was quantified under various physical conditions, including a range of temperatures and dextran molecular weights. Dextran, entrapped in cavities in the nanoparticle network, was released with a rate regulated by their molecular weights and cavity size. No release from a conventional bulk PNIPAM gel, with high crosslinking density, was observed. The rate of release from the PNIPAM-co-allylamine network was temperature-dependent, being much faster at room temperature than that at human body temperature. In contrast, release of low molecular weight dextrans from the PNIPAM-co-AA network showed a temperature-independent release profile. These nanoparticle networks have several advantages over conventional bulk gels for controlling the release of high molecular weight biomolecules. PMID:14744482

  9. Proceedings: Neurohormonal control of prolactin release.

    PubMed

    Deis, R P; Alonso, N; Vermouth, N T

    1973-01-01

    Neurohomonal control of prolactin release was studied in pseudopregnant and pregnant rats. Nembutal administered at 1300 hours on Day 3 of pseudopregnancy prevented prolactin release which normally occurred at 1700 hours of the same day. Antiestrogen administered the day before did not prevent prolactin release but ovariectomy did. Estrogen administered immediately after ovariectomy did not restore prolactin secretion; however, progesterone on Day 3 in the ovariectomized-estrogen treated induced an increase in prolactin at 1700 hours. Progesterone was capable of increasing prolactin release the first 5 days of pseudopregnancy but not Days 6-12 when prolactin values were low. A similar effect was seen the first 7 days of pregnancy. Progesterone, but not estrogen, modified prolactin values on Day 9 at 1700 hours. Ovariectomy on Day 19 of pregnancy induced prolactin release within 4 hours and persisted for 58 hours. Progesterone administration immediately after ovariectomy prevented prolactin release for a few hours. These results suggest that the regulation of prolactin release by the central nervous system depends on the circulating estrogen/progesterone ratio, since estrogen facilitated prolactin release when plasma progesterone was low and progesterone induced prolactin release when adequated levels of estrogen existed, but exerted an inhibitory action when estrogen was not present. PMID:4795042

  10. RAPID DOPAMINE TRANSMISSION WITHIN THE NUCLEUS ACCUMBENS DRAMATICALLY DIFFERS FOLLOWING MORPHINE AND OXYCODONE DELIVERY

    PubMed Central

    Mabrouk, Omar S.; Lovic, Vedran; Singer, Bryan F.; Kennedy, Robert T.; Aragona, Brandon J.

    2014-01-01

    While most drugs of abuse increase dopamine neurotransmission, rapid neurochemical measurements show that different drugs evoke distinct dopamine release patterns within the nucleus accumbens. Rapid changes in dopamine concentration following psychostimulant administration have been well studied; however, such changes have never been examined following opioid delivery. Here, we provide novel measures of rapid dopamine release following intravenous infusion of two opioids, morphine and oxycodone, in drug naïve rats using fast-scan cyclic voltammetry and rapid (1 min) microdialysis coupled with mass spectrometry. In addition to measuring rapid dopamine transmission, microdialysis HPLC-MS measures changes in GABA, glutamate, monoamines, monoamine metabolites, and several other neurotransmitters. Although both opioids increased dopamine release in the nucleus accumbens, their patterns of drug-evoked dopamine transmission differed dramatically. Oxycodone evoked a robust and stable increase in dopamine concentration and a robust increase in the frequency and amplitude of phasic dopamine release events. Conversely, morphine evoked a brief (~ 1 min) increase in dopamine that was coincident with a surge in GABA concentration and then both transmitters returned to baseline levels. Thus, by providing rapid measures of neurotransmission, this study reveals previously unknown differences in opioid-induced neurotransmitter signaling. Investigating these differences may be essential for understanding how these two drugs of abuse could differentially usurp motivational circuitry and powerfully influence behavior. PMID:25208732

  11. Encapsulation of ketoprofen for controlled drug release.

    PubMed

    Arida, Adi I; Al-Tabakha, Moawia M

    2007-04-01

    Ketoprofen particles were encapsulated with polyions and gelatin to control the release of the drug in aqueous solutions. Charged linear polyions and gelatin were alternatively deposited on 6 microm drug microcrystals through layer-by-layer (LbL) assembly. Sequential layers of poly(dimethyldiallyl ammonium chloride) (PDDA) and poly(styrenesulfonate) (PSS) were followed by adsorption of two to six gelatin/PSS bilayers with corresponding capsule wall thicknesses ranging from 41 to 111 nm. The release of Ketoprofen from the coated microparticles was measured in aqueous solutions of pH 1.4, 4.1, and 7.4. The release rate has changed at these different pH values. At pH 7.4 the release rate of Ketoprofen from the encapsulated particles was less by 107 times compared to uncoated Ketoprofen. The results provide a method of achieving prolonged drug release through self-assembly of polymeric shells on drug crystals. PMID:17098404

  12. Controlling protein release using biodegradable microparticles

    NASA Astrophysics Data System (ADS)

    Kline, Benjamin Patrick

    Research in the field of protein therapeutics has exploded over the past decade and continues to grow in both academia and in industry. Protein drugs have advantages of being highly specific and highly active making them coveted targets for high profile disease states like cancer and multiple sclerosis. Unfortunately, their many advantages are complemented by their obstacles. Because proteins are highly active and highly specific, the window between efficacy and toxicity is very narrow and drug development can be long and arduous. In addition, protein activity is dependent on its specific folding conformation that is easily disrupted by a variety of development processes. This research aimed to identify microparticle formulations to control protein release and also to determine which formulation parameters affected burst release, encapsulation, and steady-state release the most. It was found that polymer type and composition were two of the most important factors. Long-term controlled release of bovine serum albumin (BSA) was achieved as well as a wide variety of release profiles. A method was identified for micronizing protein at low cost to retain activity and coacervation was evaluated as a method for preparing protein loaded microspheres. This research provides a basis from which researchers can create better controlled release formulations for future protein therapeutics.

  13. Co-administration of morphine and oxycodone vaccines reduces the distribution of 6-monoacetylmorphine and oxycodone to brain in rats

    PubMed Central

    Pravetoni, M; Raleigh, MD; Le Naour, M; Tucker, AM; Harmon, TM; Jones, JM; Birnbaum, AK; Portoghese, PS; Pentel, PR

    2012-01-01

    Opioid conjugate vaccines have shown promise in animal models as a potential treatment for opioid addiction. Individual vaccines are quite specific and each targets only a limited number of structurally similar opioids. Since opioid users can switch or transition between opioids, we studied a bivalent immunization strategy of combining 2 vaccines that could target several of the most commonly abused opioids; heroin, oxycodone and their active metabolites. Morphine (M) and oxycodone (OXY) haptens were conjugated to keyhole limpet hemocyanin (KLH) through tetraglycine (Gly)4 linkers at the C6 position. Immunization of rats with M-KLH alone produced high titers of antibodies directed against heroin, 6-monoacetylmorphine (6-MAM) and morphine. Immunization with OXY-KLH produced high titers of antibodies against oxycodone and oxymorphone. Immunization with the bivalent vaccine produced consistently high antibody titers against both immunogens. Bivalent vaccine antibody titers against the individual immunogens were higher than with the monovalent vaccines alone owing, at least in part, to cross-reactivity of the antibodies. Administration of a single concurrent intravenous dose of 6-MAM and oxycodone to rats immunized with the bivalent vaccine increased 6-MAM, morphine and oxycodone retention in serum and reduced the distribution of 6-MAM and oxycodone to brain. Vaccine efficacy correlated with serum antibody titers for both monovalent vaccines, alone or in combination. Efficacy of the individual vaccines was not compromised by their combined use. Consistent with the enhanced titers in the bivalent group, a trend toward enhanced pharmacokinetic efficacy with the bivalent vaccine was observed. These data support the possibility of co-administering two or more opioid vaccines concurrently to target multiple abusable opioids without compromising the immunogenicity or efficacy of the individual components. PMID:22583811

  14. Controlled release fertilizer workshop, 1991: Proceedings

    SciTech Connect

    Scheib, R.M.

    1991-11-01

    Over the last 20 years the Tennessee Valley Authority's National Fertilizer and Environmental Research Center (NFERC) has carried out a number of programs to develop controlled release fertilizers. They pioneered the development and commercialization of sulfur coated urea and conducted extensive research in an attempt to develop an economical synthesis for oxamide. In recent years there has developed an increasing interest in the environmental impact of fertilizers, particularly on the potential for ground water contamination by nitrate derived from fertilizer materials. In response to this interest NFERC's Chemical Research Department organized a five member Controlled Release Fertilizer (CRF) Team to reassess the potential for controlled release materials in agriculture with a view to minimizing any adverse environmental impact and increasing the efficiency of nutrient utilization by the crop. This workshop was part of that reassessment program. The workshop goals were: To determine the present status of CRF research, production and use; to assess the future needs of CRF producers and consumers; and to promote communication and exchange of information. To accomplish these goals the team invited speakers from across' the United States representing academics, experimental station researchers, fertilizer producers, environmentalists, and marketing experts to present papers.

  15. Controlled release fertilizer workshop, 1991: Proceedings

    SciTech Connect

    Scheib, R.M.

    1991-11-01

    Over the last 20 years the Tennessee Valley Authority`s National Fertilizer and Environmental Research Center (NFERC) has carried out a number of programs to develop controlled release fertilizers. They pioneered the development and commercialization of sulfur coated urea and conducted extensive research in an attempt to develop an economical synthesis for oxamide. In recent years there has developed an increasing interest in the environmental impact of fertilizers, particularly on the potential for ground water contamination by nitrate derived from fertilizer materials. In response to this interest NFERC`s Chemical Research Department organized a five member Controlled Release Fertilizer (CRF) Team to reassess the potential for controlled release materials in agriculture with a view to minimizing any adverse environmental impact and increasing the efficiency of nutrient utilization by the crop. This workshop was part of that reassessment program. The workshop goals were: To determine the present status of CRF research, production and use; to assess the future needs of CRF producers and consumers; and to promote communication and exchange of information. To accomplish these goals the team invited speakers from across` the United States representing academics, experimental station researchers, fertilizer producers, environmentalists, and marketing experts to present papers.

  16. Controlled Release Formulations of Auxinic Herbicides

    NASA Astrophysics Data System (ADS)

    Kowalski, Witold J.; Siłowiecki, Andrzej.; Romanowska, Iwona; Glazek, Mariola; Bajor, Justyna; Cieciwa, Katarzyna; Rychter, Piotr

    2013-04-01

    Controlled release formulations are applied extensively for the release of active ingredients such as plant protection agents and fertilizers in response to growing concern for ecological problems associated with increased use of plant protection chemicals required for intensive agricultural practices [1]. We synthesized oligomeric mixtures of (R,S)-3-hydroxy butyric acid chemically bonded with 2,4-D, Dicamba and MCPA herbicides (HBA) respectively, and determined their molecular structure and molecular weight dispersion by the size exclusion chromatography, proton magnetic resonance spectrometry and electro-spray ionization mass spectrometry. Further we carried out bioassays of herbicidal effectiveness of the HBA herbicides vs. series of dicotyledonous weeds and crop injury tests [2, 3, 4]. Field bioassays were accomplished according to the EPPO standards [5]. Groups of representative weeds (the development stages in the BCCH scale: 10 - 30) were selected as targets. Statistical variabilities were assessed by the Fisher LSD test for plants treated with the studied herbicides in form of HBA oligomers, the reference herbicides in form of dimethyl ammonium salts (DMA), and untreated plants. No statistically significant differences in the crop injuries caused by the HBA vs. the DMA reference formulation were observed. The effectiveness of the HBA herbicides was lower through the initial period (ca. 2 weeks) relative to the DMA salts, but a significant increase in the effectiveness of the HBA systems followed during the remaining fraction of each assay. After 6 weeks all observed efficiencies approached 100%. The death of weeds treated with the HBA herbicides was delayed when compared with the DMA reference herbicides. The delayed uptake observed for the HBA oligomers relative to the DMA salts was due to controlled release phenomena. In case of the DMA salts the total amount of active ingredients was available at the target site. By contrast, the amount of an active

  17. Electrosprayed nanoparticle delivery system for controlled release.

    PubMed

    Eltayeb, Megdi; Stride, Eleanor; Edirisinghe, Mohan; Harker, Anthony

    2016-09-01

    This study utilises an electrohydrodynamic technique to prepare core-shell lipid nanoparticles with a tunable size and high active ingredient loading capacity, encapsulation efficiency and controlled release. Using stearic acid and ethylvanillin as model shell and active ingredients respectively, we identify the processing conditions and ratios of lipid:ethylvanillin required to form nanoparticles. Nanoparticles with a mean size ranging from 60 to 70nm at the rate of 1.37×10(9) nanoparticles per minute were prepared with different lipid:ethylvanillin ratios. The polydispersity index was ≈21% and the encapsulation efficiency ≈70%. It was found that the rate of ethylvanillin release was a function of the nanoparticle size, and lipid:ethylvanillin ratio. The internal structure of the lipid nanoparticles was studied by transmission electron microscopy which confirmed that the ethylvanillin was encapsulated within a stearic acid shell. Fourier transform infrared spectroscopy analysis indicated that the ethylvanillin had not been affected. Extensive analysis of the release of ethylvanillin was performed using several existing models and a new diffusive release model incorporating a tanh function. The results were consistent with a core-shell structure. PMID:27207047

  18. Injectable controlled release depots for large molecules

    PubMed Central

    Schwendeman, Steven P.; Shah, Ronak B.; Bailey, Brittany A.; Schwendeman, Anna S.

    2014-01-01

    Biodegradable, injectable depot formulations for long-term controlled drug release have improved therapy for a number of drug molecules and led to over a dozen highly successful pharmaceutical products. Until now, success has been limited to several small molecules and peptides, although remarkable improvements have been accomplished in some of these cases. For example, twice-a-year depot injections with leuprolide are available compared to the once-a-day injection of the solution dosage form. Injectable depots are typically prepared by encapsulation of the drug in poly(lactic-co-glycolic acid) (PLGA), a polymer that is used in children every day as a resorbable suture material, and therefore, highly biocompatible. PLGAs remain today as one of the few “real world” biodegradable synthetic biomaterials used in US FDA-approved parenteral long-acting-release (LAR) products. Despite their success, there remain critical barriers to the more widespread use of PLGA LAR products, particularly for delivery of more peptides and other large molecular drugs, namely proteins. In this review, we describe key concepts in the development of injectable PLGA controlled-release depots for peptides and proteins, and then use this information to identify key issues impeding greater widespread use of PLGA depots for this class of drugs. Finally, we examine important approaches, particularly those developed in our research laboratory, toward overcoming these barriers to advance commercial LAR development. PMID:24929039

  19. Homeostatic control of presynaptic neurotransmitter release.

    PubMed

    Davis, Graeme W; Müller, Martin

    2015-01-01

    It is well established that the active properties of nerve and muscle cells are stabilized by homeostatic signaling systems. In organisms ranging from Drosophila to humans, neurons restore baseline function in the continued presence of destabilizing perturbations by rebalancing ion channel expression, modifying neurotransmitter receptor surface expression and trafficking, and modulating neurotransmitter release. This review focuses on the homeostatic modulation of presynaptic neurotransmitter release, termed presynaptic homeostasis. First, we highlight criteria that can be used to define a process as being under homeostatic control. Next, we review the remarkable conservation of presynaptic homeostasis at the Drosophila, mouse, and human neuromuscular junctions and emerging parallels at synaptic connections in the mammalian central nervous system. We then highlight recent progress identifying cellular and molecular mechanisms. We conclude by reviewing emerging parallels between the mechanisms of homeostatic signaling and genetic links to neurological disease. PMID:25386989

  20. Metabolism of Oxycodone in Human Hepatocytes from Different Age Groups and Prediction of Hepatic Plasma Clearance

    PubMed Central

    Korjamo, Timo; Tolonen, Ari; Ranta, Veli-Pekka; Turpeinen, Miia; Kokki, Hannu

    2012-01-01

    Oxycodone is commonly used to treat severe pain in adults and children. It is extensively metabolized in the liver in adults, but the maturation of metabolism is not well understood. Our aim was to study the metabolism of oxycodone in cryopreserved human hepatocytes from different age groups (3 days, 2 and 5 months, 4 years, adult pool) and predict hepatic plasma clearance of oxycodone using these data. Oxycodone (0.1, 1, and 10 μM) was incubated with hepatocytes for 4 h, and 1 μM oxycodone also with CYP3A inhibitor ketoconazole (1 μM). Oxycodone and noroxycodone concentrations were determined at several time points with liquid chromatography–mass spectrometry. In vitro clearance of oxycodone was used to predict hepatic plasma clearance, using the well-stirred model and published physiological parameters. Noroxycodone was the major metabolite in all batches and ketoconazole inhibited the metabolism markedly in most cases. A clear correlation between in vitro oxycodone clearance and CYP3A4 activity was observed. The predicted hepatic plasma clearances were typically much lower than the published median total plasma clearance from pharmacokinetic studies. The data suggests that there are no children-specific metabolites of oxycodone. Moreover, CYP3A activity seems to be the major determinant in metabolic clearance of oxycodone regardless of age group or individual variability in hepatocyte batches. PMID:22291644

  1. Temperature-Controlled Clamping and Releasing Mechanism

    NASA Technical Reports Server (NTRS)

    Rosing, David; Ford, Virginia

    2005-01-01

    A report describes the development of a mechanism that automatically clamps upon warming and releases upon cooling between temperature limits of approx. =180 K and approx. =293 K. The mechanism satisfied a need specific to a program that involved repeated excursions of a spectrometer between a room-temperature atmospheric environment and a cryogenic vacuum testing environment. The mechanism was also to be utilized in the intended application of the spectrometer, in which the spectrometer would be clamped for protection during launch of a spacecraft and released in the cold of outer space to allow it to assume its nominal configuration for scientific observations. The mechanism is passive in the sense that its operation does not depend on a control system and does not require any power other than that incidental to heating and cooling. The clamping and releasing action is effected by bolt-preloaded stacks of shape-memory-alloy (SMA) cylinders. In designing this mechanism, as in designing other, similar SMA mechanisms, it was necessary to account for the complex interplay among thermal expansion, elastic and inelastic deformation under load, and SMA thermomechanical properties.

  2. Cattle fly control using controlled-release insecticides.

    PubMed

    Tarry, D W

    1985-10-01

    Field trials were carried out from 1980 to 1984 on the use of a controlled-release pesticidal fly control technique on farms in Sussex, England, with a recurrent infectious keratoconjunctivitis problem related to fly attack. Pesticide impregnated p.v.c. ear-tags provided control of biting and disease-carrying fly species throughout the season. Over 90% control of flies, compared with untreated herds, was attained using 2 tags impregnated with cypermethrin, fenvalerate or flucythrinate, although control using a single tag was unsatisfactory. In all cases infectious keratoconjunctivitis was almost completely eliminated. PMID:4082447

  3. A rapid technique for prediction of nutrient release from controlled release fertilizers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nutrient release from soluble granular fertilizers can be modified by polymer coating to extend the total duration nutrient release up to 3 to 9 months and rate of release to match the nutrient requirement of the plant during the growing period. Hence these products are termed as “Controlled Release...

  4. 28 CFR 541.50 - Release from a control unit.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Release from a control unit. 541.50 Section 541.50 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE INSTITUTIONAL MANAGEMENT INMATE DISCIPLINE AND SPECIAL HOUSING UNITS Control Unit Programs § 541.50 Release from a control unit. (a) Only the Executive Panel may release...

  5. Molecular gels-based controlled release devices for pheromones

    Technology Transfer Automated Retrieval System (TEKTRAN)

    2-Heptanone is a volatile solvent that is effective in controlling parasitic mites (Varroa) in honeybee. Controlled-release of 2-heptanone is needed to avoid overdosing, minimize chemical usage, and provide a sustained release over a several week period. Control-release devices comprised of a reserv...

  6. Software control of intelligent drug releases using stimuli-responsive release systems and IR data communication

    NASA Astrophysics Data System (ADS)

    Sakata, Shoei; Uchida, Kumao; Kaetsu, Isao; Kita, Yoshimi; Tsuji, Daisuke

    2007-04-01

    Intelligent drug delivery systems using UV polymerized hydrogels controlled by software were developed. The conditions of drug releases such as drug concentration, timing and amount of released drug could be controlled. It was also shown that the release threshold and the program design could be modified by IR data communication.

  7. Controlled release of vancomycin from biodegradable microcapsules.

    PubMed

    Ozalp, Y; Ozdemir, N; Kocagöz, S; Hasirci, V

    2001-01-01

    Poly D,L-lactic acid (PLA) and its copolymers with glycolide PLGA 90:10 and 70:30 were polymerized under various conditions to yield polymers in the molecular weight range 12000-40000 daltons, as determined by gel permeation chromatography. Vancomycin hydrochloride was the hydrophilic drug of choice for the treatment of methicillin resistant Staphyloccoccal infections. It was microencapsulated in the synthesized polymers using water-oil-water (w/o/w) double emulsion and solvent evaporation. The influence of microcapsule preparation medium on product properties was investigated. An increase in polymer-to-drug ratio from 1:1 to 3:1 caused an increase in the encapsulation efficiency (i.e. from 44-97% with PLGA). An increase in the emulsifier (PVA) molecular weight from 14-72 kD caused an increase in encapsulation efficiency and microcapsule size. The in vitro release of vancomycin from microcapsules in phosphate buffer saline (pH 7.4) was found to be dependent on molecular weight and copolymer type. The kinetic behaviour was controlled by both diffusion and degradation. Sterilization with 60Co (2.5 Mrad) also affected the degradation rate and release profiles. Degradation of microcapsules could be seen by scanning electron microscopy, by the increase in the release rate from PLA and by the decrease in the Tg values of microcapsules. In vitro bactericidal effects of the microcapsule formulations on S. aureus were determined with a special diffusion cell after the preparations had been sterilized, and were found to have bactericidal effects lasting for 4 days. PMID:11201344

  8. Sex differences in responsiveness to the prescription opioid oxycodone in mice.

    PubMed

    Collins, Devon; Reed, Brian; Zhang, Yong; Kreek, Mary Jeanne

    2016-09-01

    Over-prescription and increased nonmedical use of oxycodone has become a major concern. Despite its increased use, preclinical data concerning oxycodone's effects are still limited, especially in rodent models. To address this, we examined oxycodone's effects on place preference, locomotor activation, corticosterone levels, and thermal analgesia across a range of doses (between 0.3 and 10mg/kg) in gonadally intact, adult male and female C57BL/6J mice. Males and females showed oxycodone-induced conditioned place preference and did not show significant between-sex differences in their place preference behavior. During both CPP conditioning sessions and open field assay, locomotor activity was increased by 1, 3, and 10mg/kg oxycodone in females and by 3 and 10mg/kg oxycodone in males. Plasma corticosterone levels were higher in females (compared to males) at baseline as well as following acute oxycodone injection and open field testing. The time course of oxycodone-induced analgesia was similar in males and females, however the total antinociceptive effect (AUC0-120min) was larger in males compared to females at the highest dose tested (10mg/kg). Taken together, these data suggest that male and female mice are modestly different in their responses to oxycodone. PMID:27316549

  9. Controlled release of water-soluble herbicides

    SciTech Connect

    Riggle, B.D.

    1985-01-01

    Pine kraft lignin was used to control the release of metribuzin (4-amino-6-tert-butyl-3-(methylthio)-as-triazin-5(4H)-one) and alachlor (2-chloro-2',6'-diethyl-N-methoxy-methyl acetanalide). Soil thin layer chromatography (TLC) analysis using /sup 14/C-metribuzin and /sup 14/C-alachlor demonstrated that NB-5203-58 series and PC940 series kraft lignins could retard the mobility of both herbicides after multiple soil TLC plate developments with water. Soil column chromatography analysis demonstrated that PC940C could retard the mobility of both herbicides after soil column water leaching by positioning the herbicides in the top portion of the soil column where the PC940C-herbicide mixture had been applied. There was a concentration effect where, as more PC940C was used, more /sup 14/C-labelled herbicide was retained in the top portion of the soil columns. Soil column chromatography and soil TLC plate analysis demonstrated that /sup 3/H-PC940C was immobile. Finally, PC940C significantly reduced metribuzin related phytotoxicity to field and greenhouse grown soybeans (Glycine max (L.) Merr.) which had been treated with PC940C rates of 0.77 and 1.15 L/ha and metribuzin rates of 0.42 and 0.84 kg/ha. The results for /sup 14/C-metribuzin and /sup 14/C-alachlor as well as the reduction in metribuzin related phytotoxicity to soybeans suggests that PC940C can effectively control the release of metribuzin and alachlor.

  10. Tailoring nanoarchitectonics to control the release profile of payloads.

    PubMed

    Jiang, Shuai; Lv, Liping; Li, Qifeng; Wang, Junwei; Landfester, Katharina; Crespy, Daniel

    2016-06-01

    We demonstrate here that the control over the release rate of payloads and on the selectivity of the release can be achieved by designing nanomaterials with a hierarchical structure. Redox-responsive silica nanocapsules are first synthesized to allow for an accelerated release of the corrosion inhibitor 2-mercaptobenzothiazole as a payload upon chemical reduction and retarded release upon oxidation. In a second step, we embedded the nanocapsules into nanofibers by colloid-electrospinning, yielding a hierarchical composite structure. Remarkably, the encapsulation of the nanocapsules in the fibers provides two decisive advantages that are a higher selectivity of the release and a higher control over the release rate of payloads. PMID:27198762

  11. A Rapid Test for Prediction of Nutrient Release from Controlled Release Fertilizers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nutrient release from soluble granular fertilizers can be modified by polymer coating. The coating technology can be fine-tuned to change the duration (3 to 9 months) and rate of nutrient release, hence these products are termed as controlled release fertilizers (CRF). There is a need to develop a r...

  12. Multifunctional Magnetoliposomes for Sequential Controlled Release.

    PubMed

    Salvatore, Annalisa; Montis, Costanza; Berti, Debora; Baglioni, Piero

    2016-08-23

    The simultaneous or sequential delivery of multiple therapeutic active principles to a specific target is one of the main challenges of nanomedicine. This goal requires the construction of complex devices often extremely time and cost consuming. Supramolecular self-assemblies, with building blocks of different nature, each providing a specific function to the final construct, can combine a facile synthetic route with a high tunability and structural control. In this study we provide the proof-of-principle of a drug delivery system, DDS, constituted of (i) liposomes, providing a fully biocompatible lipid scaffold suitable to host both hydrophobic and hydrophilic drugs; (ii) a double-stranded DNA conjugated with a cholesteryl unit that spontaneously inserts into the lipid membrane; and (iii) hydrophobic and hydrophilic superparamagnetic iron oxide nanoparticles (SPIONs) embedded inside the lipid membrane of liposomes or connected to the DNA, respectively. Upon application of an alternating magnetic field, the SPIONs can trigger, through thermal activation, the release of a DNA strand or of the liposomal payload, depending on the frequency and the application time of the field, as proved by both steady-state and time-resolved fluorescence studies. This feature is due to the different localization of the two kinds of SPIONS within the construct and demonstrates the feasibility of a multifunctional DDS, built up from self-assembly of biocompatible building blocks. PMID:27504891

  13. Bromfenac sodium, acetaminophen/oxycodone, ibuprofen, and placebo for relief of postoperative pain.

    PubMed

    Johnson, G H; Van Wagoner, J D; Brown, J; Cooper, S A

    1997-01-01

    The objective of this double-masked, parallel-group, multicenter, inpatient study was to compare bromfenac with an acetaminophen/oxycodone combination and ibuprofen in patients who had pain due to abdominal gynecologic surgery. In the 8-hour, single-dose phase, 238 patients received single oral doses of bromfenac (50 or 100 mg), acetaminophen 650 mg/oxycodone 10 mg, ibuprofen 400 mg, or placebo. In the multiple-dose phase, 204 patients received bromfenac, acetaminophen/oxycodone, or ibuprofen for up to 5 days. In the single-dose phase, both bromfenac doses produced peak analgesic responses equivalent to acetaminophen/oxycodone, but the responses to bromfenac were longer lasting. Bromfenac produced significantly better overall (8-hour) analgesic summed scores than acetaminophen/oxycodone. Ibuprofen was less efficacious than the other analgesics. The remedication rate was lower in both bromfenac groups than in the other treatment groups. The acetaminophen/oxycodone group reported more somnolence and vomiting. Single doses of bromfenac provided analgesia at least equivalent to that of the acetaminophen/oxycodone combination, with a longer duration of action. Both doses of bromfenac and acetaminophen/oxycodone were superior to ibuprofen in this study. PMID:9220215

  14. Efficacy and tolerability of oral oxycodone and oxycodone/naloxone combination in opioid-naïve cancer patients: a propensity analysis

    PubMed Central

    Lazzari, Marzia; Greco, Maria Teresa; Marcassa, Claudio; Finocchi, Simona; Caldarulo, Clarissa; Corli, Oscar

    2015-01-01

    Background World Health Organization step III opioids are required to relieve moderate-to-severe cancer pain; constipation is one of the most frequent opioid-induced side effects. A fixed combination, prolonged-release oxycodone/naloxone (OXN), was developed with the aim of reducing opioid-related gastrointestinal side effects. The objective of this study was to compare the efficacy and safety of prolonged-release oxycodone (OXY) alone to OXN in opioid-naïve cancer patients with moderate-to-severe pain. Methods Propensity analysis was utilized in this observational study, which evaluated the efficacy, safety, and quality of life. Results Out of the 210 patients recruited, 146 were matched using propensity scores and included in the comparative analysis. In both groups, pain intensity decreased by ≈3 points after 60 days, indicating comparable analgesic efficacy. Responder rates were similar between groups. Analgesia was achieved and maintained with similarly low and stable dosages over time (12.0–20.4 mg/d for OXY and 11.5–22.0 mg/d for OXN). Bowel Function Index (BFI) and laxative use per week improved from baseline at 30 days and 60 days in OXN recipients (−16, P<0.0001 and −3.5, P=0.02, respectively); BFI worsened in the OXY group. The overall incidence of drug-related adverse events was 28.9% in the OXY group and 8.2% in the OXN group (P<0.01); nausea and vomiting were two to five times less frequent with OXN. Quality of life improved to a significantly greater extent in patients receiving OXN compared to OXY (increase in Short Form-36 physical component score of 7.1 points vs 3.2 points, respectively; P<0.001). Conclusion In patients with chronic cancer pain, OXN provided analgesic effectiveness that is similar to OXY, with early and sustained benefits in tolerability. The relationship between responsiveness to OXN and clinical characteristics is currently being investigated. PMID:26586937

  15. 28 CFR 541.50 - Release from a control unit.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Release from a control unit. 541.50 Section 541.50 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE INSTITUTIONAL MANAGEMENT INMATE DISCIPLINE AND SPECIAL HOUSING UNITS Control Unit Programs § 541.50 Release from a control...

  16. Tailoring nanoarchitectonics to control the release profile of payloads

    NASA Astrophysics Data System (ADS)

    Jiang, Shuai; Lv, Liping; Li, Qifeng; Wang, Junwei; Landfester, Katharina; Crespy, Daniel

    2016-06-01

    We demonstrate here that the control over the release rate of payloads and on the selectivity of the release can be achieved by designing nanomaterials with a hierarchical structure. Redox-responsive silica nanocapsules are first synthesized to allow for an accelerated release of the corrosion inhibitor 2-mercaptobenzothiazole as a payload upon chemical reduction and retarded release upon oxidation. In a second step, we embedded the nanocapsules into nanofibers by colloid-electrospinning, yielding a hierarchical composite structure. Remarkably, the encapsulation of the nanocapsules in the fibers provides two decisive advantages that are a higher selectivity of the release and a higher control over the release rate of payloads.We demonstrate here that the control over the release rate of payloads and on the selectivity of the release can be achieved by designing nanomaterials with a hierarchical structure. Redox-responsive silica nanocapsules are first synthesized to allow for an accelerated release of the corrosion inhibitor 2-mercaptobenzothiazole as a payload upon chemical reduction and retarded release upon oxidation. In a second step, we embedded the nanocapsules into nanofibers by colloid-electrospinning, yielding a hierarchical composite structure. Remarkably, the encapsulation of the nanocapsules in the fibers provides two decisive advantages that are a higher selectivity of the release and a higher control over the release rate of payloads. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr00917d

  17. Environmental Release Prevention and Control Plan

    SciTech Connect

    Mamatey, A.; Arnett, M.

    1997-10-01

    During the history of SRS, continual improvements in facilities, process, and operations, and changes in the site`s mission have reduced the amount of radioactive liquid releases. In the early years of SRS (1958 to 1965), the amount of tritium discharged to the Savannah River averaged approximately 61,000 curies a year. During the mid-1980`s (1983 to 1988), liquid releases of tritium averaged 27,000 curies a year. By 1996, liquid releases of tritium are projected to be just 3000 curies for the year. This large projected decrease is the result of the planned shut-down of all reactors and the anticipated significant decline in the amount of tritium migrating from the site seepage basins and the Solid Waste Disposal Facility.

  18. [Nutrient release characteristics and use efficiency of slow- and controlled release fertilizers].

    PubMed

    Duan, Lu-Lu; Zhang, Min; Liu, Gang; Shang, Zhao-Cong; Yang, Yi

    2009-05-01

    Water extraction method and soil incubation method were used to study the nutrient release characteristics of four slow- and controlled release fertilizers (CRF1, CRF2, SCU, and IBDU), and pot experiment was conducted to assess the effects of the release characteristics on the nutrient requirements of canola (Brassica napus L.). The nutrient release curves of test fertilizers in water were S pattern for CRF1 and CRF2, burst pattern for SCU, and reverse L pattern for IBDU. The nutrient release characteristics of the four fertilizers in water and in soil all fitted binomial equations, suggesting that there existed some similarities in the nutrient release in the two media. The nutrient uptake and biomass of canola plants treated with CRF1 and CRF2 were significantly higher than those treated with SCU and IBDU, and CRF2 had the greatest effect. The nutrient release curves of CRF1 and CRF2 accorded more closely with the nutrient requirements of canola. PMID:19803169

  19. Design of an actively controlled snow ski release binding.

    PubMed

    Hull, M L; Allen, K W

    1981-08-01

    A new electronic ski binding has been designed which may better protect skiers from lower extremity injuries. A four-step procedure for developing binding release criteria aimed at preventing specific injuries is outlined. Using simplified biomechanical models, the release criteria for tibia fracture in both torsion and flexion are derived. A binding design which embodies the derived release criteria is described. The binding consists of three subsystems: 1) a dynamometer, 2) an analog computer controller, and 3) an electromechanical release mechanism. The strain gage dynamometer directly measures torsion and bending moments between the boot and ski. An analog computer controlled processes dynamometer signals. Dual release mode capability is achieved by parallel solution of differential equations which model the leg in both medial-lateral rotation and flexion. When the model solution reaches a critical value, the controller actuates the release mechanism. The release mechanism incorporates a unique closed circuit hydraulic system which rigidly locks the boot to the ski until release. Laboratory tests on a prototype confirm that the computer-controlled binding prevents inadvertent release under noninjurious high-magnitude, short-duration loads but releases before quasi-static loads reach injurious levels. PMID:7278190

  20. Overview study of LNG release prevention and control systems

    SciTech Connect

    Pelto, P.J.; Baker, E.G.; Holter, G.M.; Powers, T.B.

    1982-03-01

    The liquefied natural gas (LNG) industry employs a variety of release prevention and control techniques to reduce the likelihood and the consequences of accidental LNG releases. A study of the effectiveness of these release prevention and control systems is being performed. Reference descriptions for the basic types of LNG facilities were developed. Then an overview study was performed to identify areas that merit subsequent and more detailed analyses. The specific objectives were to characterize the LNG facilities of interest and their release prevention and control systems, identify possible weak links and research needs, and provide an analytical framework for subsequent detailed analyses. The LNG facilities analyzed include a reference export terminal, marine vessel, import terminal, peakshaving facility, truck tanker, and satellite facility. A reference description for these facilities, a preliminary hazards analysis (PHA), and a list of representative release scenarios are included. The reference facility descriptions outline basic process flows, plant layouts, and safety features. The PHA identifies the important release prevention operations. Representative release scenarios provide a format for discussing potential initiating events, effects of the release prevention and control systems, information needs, and potential design changes. These scenarios range from relatively frequent but low consequence releases to unlikely but large releases and are the principal basis for the next stage of analysis.

  1. Layered superhydrophobic meshes for controlled drug release.

    PubMed

    Falde, Eric J; Freedman, Jonathan D; Herrera, Victoria L M; Yohe, Stefan T; Colson, Yolonda L; Grinstaff, Mark W

    2015-09-28

    Layered superhydrophobic electrospun meshes composed of poly(ε-caprolactone) (PCL) and poly(glycerol monostearate-co-ε-caprolactone) (PGC-C18) are described as a local source of chemotherapeutic delivery. Specifically, the chemotherapeutic agent SN-38 is incorporated into a central 'core' layer, between two 'shield' layers of mesh without drug. This mesh is resistant to wetting of the surface and throughout the bulk due to the pronounced hydrophobicity imparted by the high roughness of a hydrophobic polymer, PGC-C18. In serum solution, these meshes exhibit slow initial drug release over 10days corresponding to media infiltrating the shield layer, followed by steady release over >30days, as the drug-loaded core layer is wetted. This sequence of events is supported by X-ray computed tomography imaging of a contrast agent solution infiltrating the mesh. In vitro cytotoxicity data collected with Lewis Lung Carcinoma (LLC) cells are consistent with this release profile, remaining cytotoxic for over 20days, longer than the unlayered version. Finally, after subcutaneous implantation in rats, histology of meshes with and without drug demonstrated good integration and lack of adverse reaction over 28days. The drug release rates, robust superhydrophobicity, in vitro cytotoxicity of SN-38 loaded meshes, and compatibility provide key design parameters for the development of an implantable chemotherapeutic-loaded device for the prevention of local lung cancer recurrence following surgical resection. PMID:26160309

  2. 77 FR 12621 - Importer of Controlled Substances; Notice of Registration; Mylan Pharmaceuticals Inc.

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-01

    ... FR 81978, Mylan Pharmaceuticals, Inc., 781 Chestnut Ridge Road, Morgantown, West Virginia 26505, made... following basic classes of controlled substances: Drug Schedule Methylphenidate (1724) II Oxycodone...

  3. Nitrogen Release in Different Soils Amended with Controlled-Release Fertilizers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nitrogen (N) release from two controlled-release N fertilizers (CRNFs) (Arborite® and ESN®) and two traditional N fertilizers (urea [(NH2)2CO)] and ammonium urea nitrate (UAN) [(NH2)2CO, NH4NO3]) in three soil types of North Carolina was measured throughout a 12 week laboratory incubation. Treatment...

  4. NUTRIENT RELEASE CHARACTERISTICS FROM FOUR TYPES OF CONTROLLED-RELEASE FERTILIZERS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Release patterns of ammonium, nitrate, phosphorous, potassium, calcium, magnesium, iron, manganese, and zinc were measured during an eleven month period for four types of Controlled Release Fertilizers (CRF): Apex 17-5-11, Multicote 17-5-11, Nutricote 18-6-8, and Osmocote 24-4-9. Rate of fertilizer...

  5. Electrospinning nanofibers for controlled drug release

    NASA Astrophysics Data System (ADS)

    Banik, Indrani

    Electrospinning is the most widely studied technique for the synthesis of nanofibers. Electrospinning is considered as one of the technologies that can produce nanosized drugs incorporated in polymeric nanofibers. In vitro and in vivo studies have demonstrated that the release rates of drugs from these nanofiber formulations are enhanced compared to those from original drug substance. This technology has the potential for enhancing the oral delivery of poorly soluble drugs. The electrospun mats were made using Polycaprolactone/PCL, Poly(DL-lactide)/PDL 05 and Poly(DL-lactide-co-glycolide)/PLGA. The drugs incorporated in the electrospun fibers were 5-Fluorouracil and Rapamycin. The evidence of the drugs being embedded in the polymers was obtained by scanning electron microscopy (SEM), Raman and infrared spectroscopy. The release of 5-Fluorouracil and Rapamycin were followed by UV-VIS spectroscopy.

  6. Release and control of hydrogen sulfide during sludge thermal drying

    SciTech Connect

    Weng, Huanxin; Dai, Zhixin; Ji, Zhongqiang; Gao, Caixia; Liu, Chongxuan

    2015-04-15

    The release of hydrogen sulfide (H2S) during sludge drying is a major environmental problem because of its toxicity to human health. A series of experiments were performed to investigate the mechanisms and factors controlling the H2S release. Results of this study show that: 1) the biomass and activity of sulfate-reducing bacteria (SRB) in sludge were the major factors controlling the amount of H2S release, 2) the sludge drying temperature had an important effect on both the extent and the timing of H2S release from the sludge, and 3) decreasing sludge pH increased the H2S release. Based on the findings from this study, a new system that integrates sludge drying and H2S gas treatment was developed to reduce the amount of H2S released from sludge treatments.

  7. Controlled release of fragrant molecules with visible light.

    PubMed

    Wang, Zhuozhi; Johns, Valentine K; Liao, Yi

    2014-11-01

    Controlled release of odorous molecules is the key to digital scent technology which will add another dimension to electronics. Photorelease is a cold mechanism that promises better temporal and spatial control than thermal release. Herein we report a novel material composed of an acid-sensitive polymer carrying a fragrant aldehyde and a reversible metastable-state photoacid. It releases the fragrant molecule under visible light, and stops releasing it after the light is turned off. A metastable-state photoacid with a fast reverse-reaction rate was developed to quickly stop the release after irradiation. Both the carrier polymer and the photoacid can be reused after all the fragrant molecules have been released. The material combines the advantages of visible-light activity, fast on/off rate, easy preparation, and recyclability, and thus is promising for digital scent technology. PMID:25284277

  8. 3D hybrid wound devices for spatiotemporally controlled release kinetics.

    PubMed

    Ozbolat, Ibrahim T; Koc, Bahattin

    2012-12-01

    This paper presents localized and temporal control of release kinetics over 3-dimensional (3D) hybrid wound devices to improve wound-healing process. Imaging study is performed to extract wound bed geometry in 3D. Non-Uniform Rational B-Splines (NURBS) based surface lofting is applied to generate functionally graded regions. Diffusion-based release kinetics model is developed to predict time-based release of loaded modifiers for functionally graded regions. Multi-chamber single nozzle solid freeform dispensing system is used to fabricate wound devices with controlled dispensing concentration. Spatiotemporal control of biological modifiers thus enables a way to achieve target delivery to improve wound healing. PMID:22672934

  9. Preparation, characterization and optimization of glipizide controlled release nanoparticles

    PubMed Central

    Emami, J.; Boushehri, M.S. Shetab; Varshosaz, J.

    2014-01-01

    The purpose of the present study was to develop glipizide controlled release nanoparticles using alginate and chitosan thorough ionotropic controlled gelation method. Glipizide is a frequently prescribed second generation sulfonylurea which lowers the blood glucose in type-two diabetics. Quick absorption of the drug from the gastrointestinal tract along with short half- life of elimination makes it a good candidate for controlled release formulations. Alginate-chitosan nanoparticles (ACNP) are convenient controlled delivery systems for glipizide, due to both the release limiting properties of the system, and the bioadhesive nature of the polymers. In the present study, glipizide loaded alginate-chitosan nanoparticles (GlACNP) were prepared, and the particle characteristics including particle size (PS), zeta potential (ZP), entrapment efficiency (EE%), loading percent (LP), and mean release time (MRT), as well as the morphology of the nanoparticles, the drug-excipient compatibility, and the release kinetics along with the drug diffusion mechanism were evaluated. The results suggested that ionotropic controlled gelation method offers the possibility of preparing the nanoparticles in mild conditions in an aqueous environment, and can lead to the preparation of particles with favorable size, controlled release characteristics, and high entrapment efficiency, serving as a convenient delivery system for glipizide. The particle and release characteristics can be efficiently optimized using the Box-Behnken design. Based on the findings of the present study, it is expected that this novel formulation be a superior therapeutic alternative to the currently available glipizide delivery systems. PMID:25657802

  10. Preparation, characterization and optimization of glipizide controlled release nanoparticles.

    PubMed

    Emami, J; Boushehri, M S Shetab; Varshosaz, J

    2014-01-01

    The purpose of the present study was to develop glipizide controlled release nanoparticles using alginate and chitosan thorough ionotropic controlled gelation method. Glipizide is a frequently prescribed second generation sulfonylurea which lowers the blood glucose in type-two diabetics. Quick absorption of the drug from the gastrointestinal tract along with short half- life of elimination makes it a good candidate for controlled release formulations. Alginate-chitosan nanoparticles (ACNP) are convenient controlled delivery systems for glipizide, due to both the release limiting properties of the system, and the bioadhesive nature of the polymers. In the present study, glipizide loaded alginate-chitosan nanoparticles (GlACNP) were prepared, and the particle characteristics including particle size (PS), zeta potential (ZP), entrapment efficiency (EE%), loading percent (LP), and mean release time (MRT), as well as the morphology of the nanoparticles, the drug-excipient compatibility, and the release kinetics along with the drug diffusion mechanism were evaluated. The results suggested that ionotropic controlled gelation method offers the possibility of preparing the nanoparticles in mild conditions in an aqueous environment, and can lead to the preparation of particles with favorable size, controlled release characteristics, and high entrapment efficiency, serving as a convenient delivery system for glipizide. The particle and release characteristics can be efficiently optimized using the Box-Behnken design. Based on the findings of the present study, it is expected that this novel formulation be a superior therapeutic alternative to the currently available glipizide delivery systems. PMID:25657802

  11. A Review: Controlled release systems for agricultural and food applications

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Controlled release systems are widely used in numerous applications. Polymers from natural resources, such as pectin, starch, zein and poly(lactic acid) have been used to construct carriers of bioactive substances and deliver them in a designed manner. The retention and release of volatile fragrance...

  12. Best Practices for Controlling Lead and Copper Release

    EPA Science Inventory

    Presentation draft, covering summary of current state-of-the-art knowledge for the best treatment strategies for minimizing lead release and controlling copper release. The presentation is intended to aid with compliance with the Lead and Copper Rule, but also provide a guide to...

  13. Controlled Release of Imidacloprid from Poly Styrene-Diacetone - Nanoformulation

    NASA Astrophysics Data System (ADS)

    Qian, Kun; Guo, Yanzhen; He, Lin

    2012-01-01

    Imidacloprid is a neonicotinoids insecticide, which is important for the cash crops such as tomato, rape and so on. The conventional formulation does not only increase the loss of pesticide but also leads to environmental pollution. Controlled-release formulations of pesticide are highly desirable not only for attaining the most effective utilization of the pesticide, but also for reducing environmental pollution. Pesticide imidacloprid was incorporated in poly (styrene-diacetone crylamide)-based formulation to obtain controlled release properties, and the imidacloprid nanocontrolled release formulation was characterized by infrared (IR) and field emission scanning electron microscope (FESEM). Factors related to loading efficiency, swelling and release behaviors of the formulation were investigated. It showed that the loading efficiency could reach about 40% (w/w). The values for the diffusion exponent "n" were in the range of 0.31-0.58, which indicated that the release of imidacloprid was diffusion-controlled. The time taken for 50% of the active ingredient to be released into water, T50, was also calculated for the comparison of formulations in different conditions. The results showed that the formulation with higher temperature and more diacetone crylamide had lower value of T50, which means a quicker release of the active ingredient. This study highlighted some pieces of evidence that improved pesticide incorporation and slower release were linked to potential interactions between the pesticide and the polymer.

  14. Tunable pH-Sensitive Linker for Controlled Release.

    PubMed

    Choy, Cindy J; Geruntho, Jonathan J; Davis, Austen L; Berkman, Clifford E

    2016-03-16

    We have developed a novel pH-sensitive linker based on a phosphoramidate scaffold that can be tuned to release amine-containing drug molecules at various pH values. The pH-triggered phosphoramidate-based linkers are responsive to pH alone and do not require intracellular enzymatic action to initiate drug release. Key to the pH-triggered amine release from these linkers is a proximal acidic group (e.g., pyridinium or carboxylic acid) to promote the hydrolysis of the phosphoramidate P-N bond, presumably through an intramolecular general-acid type mechanism. Phosphoramidate hydrolysis is largely governed by the pKa of the leaving amine (e.g., primary, secondary, aniline). However, the proximity of the neighboring pyridine group attenuates the stability of the P-N bond to hydrolysis, thus allowing for control over the release of an amine from the phosphoramidate center. Based on the model scaffolds examined, phosphoramidate-based linkers could be selected for particular properties for controlled-release applications such as amine type, stability under physiological conditions, or release rates at various pH values such as intracellular endosomal conditions. The tunability of the phosphoramidate scaffold is expected to find broad applicability in various controlled drug-release applications such as antibody or small-molecule drug conjugates, drug-eluting stents, prodrug activation, as well as intracellular trafficking studies in which pH changes can trigger the release of turn-on dyes. PMID:26886721

  15. Mucoadhesive controlled release ciprofloxacin nanoparticles for pulmonary delivery

    NASA Astrophysics Data System (ADS)

    Mudumba, Sujata S.

    Controlled release of drugs to the lungs is an interesting and evolving field of research. The influence of physicochemical properties of nanoparticles on the controlled release of ciprofloxacin and in-vivo pharmacokinetics following pulmonary administration was evaluated. The physicochemical properties had an effect on encapsulation efficiency and surface charge, but no significant effect on particle size. The in-vitro release profiles of ciprofloxacin in phosphate buffered saline showed small differences over the range of physicochemical properties evaluated. The physicochemical properties of ciprofloxacin nanoparticles resulted in variable and unreliable nebulizer output using a vibrating mesh nebulizer whereas the impact on the aerosol properties of a jet nebulizer was negligible. Addition of mucoadhesive polymers in the nanoparticles had a three-fold increase in apparent half-life in rats by releasing ciprofloxacin over an extended release period on the surfaces of the lungs.

  16. PREVENTION REFERENCE MANUAL: CONTROL TECHNOLOGIES, VOLUME 2: POST-RELEASE MITIGATION MEASURES FOR CONTROLLING ACCIDENTAL RELEASES OF AIR TOXICS

    EPA Science Inventory

    The volume discusses prevention and protection measures for controlling accidental releases of air toxics. The probability of accidental releases depends on the extent to which deviations (in magnitude and duration) in the process can be tolerated before a loss of chemical contai...

  17. PREVENTION REFERENCE MANUAL: CONTROL TECHNOLOGIES, VOL. 2. POST-RELEASE MITIGATION MEASURES FOR CONTROLLING ACCIDENTAL RELEASES OF AIR TOXICS

    EPA Science Inventory

    The volume discusses prevention and protection measures for controlling accidental releases of air toxics. The probability of accidental releases depends on the extent to which deviations (in magnitude and duration) in the process can be tolerated before a loss of chemical contai...

  18. Controlled Release of Biologically Active Silver from Nanosilver Surfaces

    PubMed Central

    Liu, Jingyu; Sonshine, David A.; Shervani, Saira; Hurt, Robert H.

    2010-01-01

    Major pathways in the antibacterial activity and eukaryotic toxicity of nano-silver involve the silver cation and its soluble complexes, which are well established thiol toxicants. Through these pathways, nano-silver behaves in analogy to a drug delivery system, in which the particle contains a concentrated inventory of an active species, the ion, which is transported to and released near biological target sites. Although the importance of silver ion in the biological response to nano-silver is widely recognized, the drug delivery paradigm has not been well developed for this system, and there is significant potential to improve nano-silver technologies through controlled release formulations. This article applies elements of the drug delivery paradigm to nano-silver dissolution and presents a systematic study of chemical concepts for controlled release. After presenting thermodynamic calculations of silver species partitioning in biological media, the rates of oxidative silver dissolution are measured for nanoparticles and macroscopic foils and used to derive unified area-based release kinetics. A variety of competing chemical approaches are demonstrated for controlling the ion release rate over four orders of magnitude. Release can be systematically slowed by thiol and citrate ligand binding, formation of sulfidic coatings, or the scavenging of peroxy-intermediates. Release can be accelerated by pre-oxidation or particle size reduction, while polymer coatings with complexation sites alter the release profile by storing and release inventories of surface-bound silver. Finally, the ability to tune biological activity is demonstrated through bacterial inhibition zone assay carried out on selected formulations of controlled release nano-silver. PMID:20968290

  19. A controlled biochemical release device with embedded nanofluidic channels

    NASA Astrophysics Data System (ADS)

    Yang, Haifeng; Hong, Wei; Dong, Liang

    2012-04-01

    A controlled release device is developed by embedding nanofluidic biomolecule reservoirs into a polymer network of a stimuli-responsive hydrogel. The reservoirs are made of liquid core-polymer shell nanofibers using co-electrospinning. The mechanism of controlled release is based on buckling instability of the polymer shell under combined axial and radial compression, caused by volume changes of hydrogel responding to a specific stimulus. The device decouples releasable biomolecules from a hydrogel polymer matrix, avoiding chemical interactions between biomolecules and hydrogel polymer chains, and thus, alleviating nontrivial chemical and biological engineering design of hydrogel formulations. Temperature-sensitive hydrogel is used as a model hydrogel.

  20. Differential activation of the μ-opioid receptor by oxycodone and morphine in pain-related brain regions in a bone cancer pain model

    PubMed Central

    Nakamura, Atsushi; Hasegawa, Minoru; Minami, Kazuhisa; Kanbara, Tomoe; Tomii, Takako; Nishiyori, Atsushi; Narita, Minoru; Suzuki, Tsutomu; Kato, Akira

    2013-01-01

    Background and Purpose Bone cancer pain is chronic and often difficult to control with opioids. However, recent studies have shown that several opioids have distinct analgesic profiles in chronic pain. Experimental Approach To clarify the mechanisms underlying these distinct analgesic profiles, functional changes in the μ-opioid receptor were examined using a mouse femur bone cancer (FBC) model. Key Results In the FBC model, the Bmax of [3H]-DAMGO binding was reduced by 15–45% in the periaqueductal grey matter (PAG), region ventral to the PAG (vPAG), mediodorsal thalamus (mTH), ventral thalamus and spinal cord. Oxycodone (10−8–10−5 M) and morphine (10−8–10−5 M) activated [35S]-GTPγS binding, but the activation was significantly attenuated in the PAG, vPAG, mTH and spinal cord in the FBC model. Interestingly, the attenuation of oxycodone-induced [35S]-GTPγS binding was quite limited (9–26%) in comparison with that of morphine (46–65%) in the PAG, vPAG and mTH, but not in the spinal cord. Furthermore, i.c.v. oxycodone at doses of 0.02–1.0 μg per mouse clearly inhibited pain-related behaviours, such as guarding, limb-use abnormalities and allodynia-like behaviour in the FBC model mice, while i.c.v. morphine (0.05–2.0 μg per mouse) had only partial or little analgesic effect on limb-use abnormalities and allodynia-like behaviour. Conclusion and Implications These results show that μ-opioid receptor functions are attenuated in several pain-related regions in bone cancer in an agonist-dependent manner, and suggest that modification of the μ-opioid receptor is responsible for the distinct analgesic effect of oxycodone and morphine. PMID:22889192

  1. A site-specific controlled-release system for metformin.

    PubMed

    Di Colo, Giacomo; Zambito, Ylenia; Baggiani, Andrea; Carelli, Vera; Serafini, Maria Francesca

    2005-05-01

    Oral absorption of the antihyperglycaemic agent metformin hydrochloride (MF-HCl) is confined to the upper part of the intestine, therefore rational controlled-release formulations of this drug should ensure a complete release during transit from stomach to jejunum. The aim of this study was the preparation of a system able to sustain release of high MF-HCl doses in compliance with the above requirement. Matrices (6 mm diameter; 50 mg weight) comprising varying drug-Precirol ATO 5 ratios were prepared by compression. The matrix containing 70% drug was coated on one face with Eudragit L100-55. Drug release to simulated gastric (SGF), jejunal (SJF) and ileal (SIF) fluids in sequence was studied using a modified USP rotating basket method. Release depended on drug load whereas it was independent of dissolution medium pH and hydrodynamics. Release kinetics were of radical t type and were determined by drug diffusion in aqueous pores created in the matrix by drug dissolution. An equation correlating rate-determining factors was developed, whereby the release pattern could be optimized. The half-coated matrix started release in SGF and completed it in SJF. The half-coated matrix, synchronizing drug release and matrix transit across the small intestine, may improve drug bioavailability and reduce side effects. PMID:15901345

  2. Controlled release of tocopherols from polymer blend films

    NASA Astrophysics Data System (ADS)

    Obinata, Noe

    Controlled release packaging has great potential to increase storage stability of foods by releasing active compounds into foods continuously over time. However, a major limitation in development of this technology is the inability to control the release and provide rates useful for long term storage of foods. Better understanding of the factors affecting active compound release is needed to overcome this limitation. The objective of this research was to investigate the relationship between polymer composition, polymer processing method, polymer morphology, and release properties of active compounds, and to provide proof of principle that compound release is controlled by film morphology. A natural antioxidant, tocopherol was used as a model active compound because it is natural, effective, heat stable, and soluble in most packaging polymers. Polymer blend films were produced from combination of linear low density polyethylene (LLDPE) and high density polyethylene (HDPE), polypropylene (PP), or polystyrene (PS) with 3000 ppm mixed tocopherols using conventional blending method and innovative blending method, smart blending with a novel mixer using chaotic advection. Film morphologies were visualized with scanning electron microscopy (SEM). Release of tocopherols into 95% ethanol as a food simulant was measured by UV/Visible spectrophotometry or HPLC, and diffusivity of tocopherols in the polymers was estimated from this data. Polymer composition (blend proportions) and processing methods have major effects on film morphology. Four different types of morphologies, dispersed, co-continuous, fiber, and multilayer structures were developed by either conventional extrusion or smart blending. With smart blending of fixed polymer compositions, different morphologies were progressively developed with fixed polymer composition as the number of rod rotations increased, providing a way to separate effects of polymer composition and morphology. The different morphologies

  3. Modeling controlled nutrient release from polymer coated fertilizers: diffusion release from single granules.

    PubMed

    Shaviv, Avi; Raban, Smadar; Zaidel, Elina

    2003-05-15

    A comprehensive model describing the complex and "non-Fickian" (mathematically nonlinear) nature of the release from single granules of membrane coated, controlled release fertilizers (CRFs) is proposed consisting of three stages: i. a lag period during which water penetrates the coating of the granule dissolving part of the solid fertilizer in it ii. a period of linear release during which water penetration into and release out occur concomitantly while the total volume of the granules remains practically constant; and iii. a period of "decaying release", starting as the concentration inside the granule starts to decrease. A mathematical model was developed based on vapor and nutrient diffusion equations. The model predicts the release stages in terms of measurable geometrical and chemophysical parameters such as the following: the product of granule radius and coating thickness, water and solute permeability, saturation concentration of the fertilizer, and its density. The model successfully predicts the complex and "sigmoidal" pattern of release that is essential for matching plant temporal demand to ensure high agronomic and environmental effectiveness. It also lends itself to more complex statistical formulations which account for the large variability within large populations of coated CRFs and can serve for further improving CRF production and performance. PMID:12785532

  4. Magnetic molecularly imprinted polymer for aspirin recognition and controlled release

    NASA Astrophysics Data System (ADS)

    Kan, Xianwen; Geng, Zhirong; Zhao, Yao; Wang, Zhilin; Zhu, Jun-Jie

    2009-04-01

    Core-shell structural magnetic molecularly imprinted polymers (magnetic MIPs) with combined properties of molecular recognition and controlled release were prepared and characterized. Magnetic MIPs were synthesized by the co-polymerization of methacrylic acid (MAA) and trimethylolpropane trimethacrylate (TRIM) around aspirin (ASP) at the surface of double-bond-functionalized Fe3O4 nanoparticles in chloroform. The obtained spherical magnetic MIPs with diameters of about 500 nm had obvious superparamagnetism and could be separated quickly by an external magnetic field. Binding experiments were carried out to evaluate the properties of magnetic MIPs and magnetic non-molecularly imprinted polymers (magnetic NIPs). The results demonstrated that the magnetic MIPs had high adsorption capacity and selectivity to ASP. Moreover, release profiles and release rate of ASP from the ASP-loaded magnetic MIPs indicated that the magnetic MIPs also had potential applications in drug controlled release.

  5. Liquid phase coating to produce controlled-release alginate microspheres.

    PubMed

    Chan, Lai Wah; Liu, Xiaohua; Heng, Paul Wan Sia

    2005-12-01

    This study explored a liquid phase coating technique to produce polymethyl methacrylate (PMMA)-coated alginate microspheres. Alginate microspheres with a mean diameter of 85.6 microm were prepared using an emulsification method. The alginate microspheres, as cores, were then coated with different types of PMMA by a liquid phase coating technique. The release characteristics of these coated microspheres in simulated gastric (SGF) and intestinal (SIF) fluids and the influence of drug load on encapsulation efficiency were studied. The release of paracetamol, as a model hydrophilic drug, from the coated microspheres in SGF and SIF was greatly retarded. Release rates of Eudragit RS100-coated microspheres in SGF and SIF were similar as the rate-controlling polymer coat was insoluble in both media. Drug release from Eudragit S100-coated microspheres was more sustained in SGF than in SIF, due to the greater solubility of the coating polymer in media with pH greater than 7.0. The drug release rate was affected by the core:coat ratio. Drug release from the coated microspheres was best described by the Higuchi's square root model. The liquid phase coating technique developed offers an efficient method of coating small microspheres with markedly reduced drug loss and possible controlled drug release. PMID:16423760

  6. Controlled release of diclofenac sodium in glycolipid incorporated micro emulsions.

    PubMed

    Premarathne, E P N; Karunaratne, D N; Perera, A D L Chandani

    2016-09-25

    The effect of the glycolipid, hexadecyl-β-d-glucopyranoside, incorporated in microemulsions (ME(1)) towards the enhancement of skin absorption and skin permeation of Diclofenac sodium (DS(2)) was evaluated. A Franz diffusion cell with a piece of pig's ear epidermis indicated that the optimized ME formulation with glycolipid (0.05wt%) exhibited significantly higher permeability than the conventional formulations. The releasing profiles of DS from ME formulations exhibited first order release kinetics resembling a diffusion controlled release model for the first 8h. Incorporating hexadecyl-β-D glucopyranoside in ME formulations shows significant potential as a delivery vehicle in the cosmetics and pharmaceutical industry. PMID:27477103

  7. Formulation of controlled release gellan gum macro beads of amoxicillin.

    PubMed

    Babu, R Jayachandra; Sathigari, Sateesh; Kumar, M Thilek; Pandit, J K

    2010-01-01

    Gellan gum has been reported to have wide pharmaceutical applications such as tablet binder, disintegrant, gelling agent and as a controlled release polymer. Multiparticulate delivery systems spread out more uniformly in the gastrointestinal tract and reduce the local irritation. The purpose of this study is to explore possible applicability of gellan macro beads as an oral controlled release system of a sparingly soluble drug, amoxicillin. Gellan gum beads were prepared by ionotropic gelation with calcium ions. The effect of drug loading, stirring time, polymer concentration, electrolyte (CaCl2) concentration, curing time etc. influencing the preparation of the gellan gum macro beads and the drug release from gellan gum beads were investigated in this study. Optimal preparation conditions allowed very high incorporation efficiency for amoxicillin (91%) The release kinetics of amoxicillin from gellan beads followed the diffusion model for an inert porous matrix in the order: 0.1 N HCl > phosphate buffer > distilled water. Change in curing time did not significantly affect the release rate constant, but drug concentration, polymer concentration and electrolyte concentration significantly affect the release rate of amoxicillin from the beads. The gellan macro beads may be suitable for gastro retentive controlled delivery of amoxicillin. PMID:19863487

  8. Optogenetic control of striatal dopamine release in rats

    PubMed Central

    Bass, Caroline E; Grinevich, Valentina P; Vance, Zachary B; Sullivan, Ryan P; Bonin, Keith D; Budygin, Evgeny A

    2010-01-01

    Optogenetic control over neuronal firing has become an increasingly elegant method to dissect the microcircuitry of mammalian brains. To date, examination of these manipulations on neurotransmitter release has been minimal. Here we present the first in-depth analysis of optogenetic stimulation on dopamine neurotransmission in the dorsal striatum of urethane-anesthetized rats. By combining the tight spatial and temporal resolution of both optogenetics and fast-scan cyclic voltammetry we have determined the parameters necessary to control phasic dopamine release in the dorsal striatum of rats in vivo. The kinetics of optically induced dopamine release mirror established models of electrically evoked release, indicating that potential artifacts of electrical stimulation on ion channels and the dopamine transporter are negligible. Furthermore a lack of change in extracellular pH indicates that optical stimulation does not alter blood flow. Optical control over dopamine release is highly reproducible and flexible. We are able to repeatedly evoke concentrations of dopamine release as small as a single dopamine transient (50 nM). A U-shaped frequency response curve exists with maximal stimulation inducing dopamine effluxes exceeding 500 nM. Taken together, these results have obvious implications for understanding the neurobiological basis of dopaminergic-based disorders and provide the framework to effectively manipulate dopamine patterns. PMID:20534006

  9. Antimicrobial beeswax coated polylactide films with silver control release capacity.

    PubMed

    Martínez-Abad, Antonio; Lagarón, Jose Maria; Ocio, María Jose

    2014-03-17

    Although the application of silver based antimicrobial systems is a widespread technology, its implementation in areas such as food packaging is still challenging. The present paper describes the fabrication of poly(lactic acid) (PLA) coated with beeswax with controlled release properties for sustained antimicrobial performance. Release of silver ions from the polymers was monitored voltammetrically under various conditions (surface contact, immersion in various liquid media and at different pH values) throughout at least 7days. A higher release was noted with decreasing pH while surface release was much slower than the release when immersed in liquid medium. While uncoated films demonstrated a high burst release which in some instances implied surpassing some current migration restrictions (<0.05mg/kg food), the addition of a beeswax layer allowed a sustained release of the antimicrobial compound. Increasing the thickness of the beeswax layer resulted in an increase in the water barrier properties of the films while reducing the relatively constant values of sustained release. Antimicrobial performance was correlated with the release of silver ions, indicating threshold concentrations for biocide action of <6μg/L and 9-14μg/L for surface contact and in liquid media, respectively. Either by surface contact or by immersion in growth medium or vegetable soup, the coated films displayed a strong bactericidal effect against Salmonella enterica. The application of this functional barrier thus offers the possibility of tuning the release profiles of the films to suit a specific application and puts forth the possible suitability of these materials for food packaging or other migration sensitive applications. PMID:24448276

  10. Sol-gel encapsulation for controlled drug release and biosensing

    NASA Astrophysics Data System (ADS)

    Fang, Jonathan

    The main focus of this dissertation is to investigate the use of sol-gel encapsulation of biomolecules for controlled drug release and biosensing. Controlled drug release has advantages over conventional therapies in that it maintains a constant, therapeutic drug level in the body for prolonged periods of time. The anti-hypertensive drug Captopril was encapsulated in sol-gel materials of various forms, such as silica xerogels and nanoparticles. The primary objective was to show that sol-gel silica materials are promising drug carriers for controlled release by releasing Captopril at a release rate that is within a therapeutic range. We were able to demonstrate desired release for over a week from Captopril-doped silica xerogels and overall release from Captopril-doped silica nanoparticles. As an aside, the antibiotic Vancomycin was also encapsulated in these porous silica nanoparticles and desired release was obtained for several days in-vitro. The second part of the dissertation focuses on immobilizing antibodies and proteins in sol-gel to detect various analytes, such as hormones and amino acids. Sol-gel competitive immunoassays on antibody-doped silica xerogels were used for hormone detection. Calibration for insulin and C-peptide in standard solutions was obtained in the nM range. In addition, NASA-Ames is also interested in developing a reagentless biosensor using bacterial periplasmic binding proteins (bPBPs) to detect specific biomarkers, such as amino acids and phosphate. These bPBPs were doubly labeled with two different fluorophores and encapsulated in silica xerogels. Ligand-binding experiments were performed on the bPBPs in solution and in sol-gel. Ligand-binding was monitored by fluorescence resonance energy transfer (FRET) between the two fluorophores on the bPBP. Titration data show that one bPBP has retained its ligand-binding properties in sol-gel.

  11. Continuous nanostructures for the controlled release of drugs.

    PubMed

    Venugopal, J; Prabhakaran, Molamma P; Low, Sharon; Choon, Aw Tar; Deepika, G; Dev, V R Giri; Ramakrishna, S

    2009-01-01

    The annual world wide market for controlled release of polymer systems which extends beyond drug delivery is now estimated to $60 billion and these systems are used by over 100 million people each year. It was estimated that drug delivery will play a pivotal role in approximately 40% of all pharmaceutical sales in near future. Novel methods of drug delivery will not only result in more effective and efficacious treatments but also generates new niche markets to provide greater intellectual property protection to already existing drug formulations. Recently, biodegradable electrospun polymer nanofibrous substrate as drug carrier seems to be a promising method for delivering anticancer drugs, especially in postoperative local chemotherapy. Alternatively drug release can be triggered by the environment or other external events such as changes in pH, temperature, or the presence of analyte such as glucose. In general, controlled release of polymer systems delivering drugs in the optimum dosage for long periods is to increase the efficacy of drug, reducing patient compliance. Recent research for the use of nanotechnology (nanoparticle and nanofibers) in drug delivery suggests that the technology might solve problems in the areas such as controlled release, various topical administration, gut absorption and targeted systemic delivery. This review article described the applications of polymer nanoparticles and nanofibers for loading potential drugs for the controlled release to target incurable diseases. PMID:19442191

  12. Understanding and managing the impact of HPMC variability on drug release from controlled release formulations.

    PubMed

    Zhou, Deliang; Law, Devalina; Reynolds, Judie; Davis, Lynn; Smith, Clifford; Torres, Jose L; Dave, Viraj; Gopinathan, Nishanth; Hernandez, Daniel T; Springman, Mary Kay; Zhou, Casey Chun

    2014-06-01

    The purpose of this study is to identify critical physicochemical properties of hydroxypxropyl methylcellulose (HPMC) that impact the dissolution of a controlled release tablet and develop a strategy to mitigate the HPMC lot-to-lot and vendor-to-vendor variability. A screening experiment was performed to evaluate the impacts of methoxy/hydroxypropyl substitutions, and viscosity on drug release. The chemical diversity of HPMC was explored by nuclear magnetic resonance (NMR), and the erosion rate of HPMC was investigated using various dissolution apparatuses. Statistical evaluation suggested that the hydroxypropyl content was the primary factor impacting the drug release. However, the statistical model prediction was not robust. NMR experiments suggested the existence of structural diversity of HPMC between lots and more significantly between vendors. Review of drug release from hydrophilic matrices indicated that erosion is a key aspect for both poorly soluble and soluble drugs. An erosion rate method was then developed, which enabled the establishment of a robust model and a meaningful HPMC specification. The study revealed that the overall substitution level is not the unique parameter that dictates its release-controlling properties. Fundamental principles of polymer chemistry and dissolution mechanisms are important in the development and manufacturing of hydrophilic matrices with consistent dissolution performance. PMID:24652662

  13. Can coadministration of oxycodone and morphine produce analgesic synergy in humans? An experimental cold pain study

    PubMed Central

    Grach, Michael; Massalha, Wattan; Pud, Dorit; Adler, Rivka; Eisenberg, Elon

    2004-01-01

    Aims The coadministration of subantinociceptive doses of oxycodone with morphine has recently been shown to result in a synergistic antinociceptive effect in rats. The present study was aimed to investigate the possibility that coadministration of morphine and oxycodone can produce a similar synergistic effect in humans exposed to an experimental model of cold pressor test (CPT). Methods The enriched enrolment design was used to exclude ‘stoic’ and ‘placebo responders’ in a single-blind fashion. ‘Nonstoic’, placebo ‘nonresponder’ female volunteers (n = 30) were randomly assigned to receive 0.5 mg kg−1 oral morphine sulphate, 0.5 mg kg−1 oral oxycodone hydrochloride, and the combination of 0.25 mg kg−1 morphine sulphate with 0.25 mg kg−1 oxycodone hydrochloride, 1 week apart from each other, in a double-blind crossover design. Latency to pain onset (threshold), pain intensity (VAS), and pain tolerance (time until removal of the hand from the water) were measured six times over a 3-h period, subsequent to the administration of each medication, and were used to assess their antinociceptive effect. Results The combination produced a significantly higher effect on latency to pain onset than that of morphine alone [difference in mean postbaseline value 2.2; 95% confidence interval (CI) 0.48, 3.9; P = 0.01] but the effect was nonsignificantly smaller that that of oxycodone alone. Similarly, the effect of the combination on pain tolerance was significantly larger than that of morphine alone (combination difference 8.4; 95% CI 2.5, 14.3; P = 0.007), whereas oxycodone alone caused a nonsignificantly larger effect than that of the combination treatment. Comparisons of pain magnitude failed to show any significant differences between the three treatments. Conclusions These results indicate that at the doses tested, morphine and oxycodone do not produce synergistic antinociceptive effects in healthy humans exposed to the CPT. PMID:15327582

  14. Application of controlled nutrient release to permeable reactive barriers.

    PubMed

    Freidman, Benjamin L; Gras, Sally L; Snape, Ian; Stevens, Geoff W; Mumford, Kathryn A

    2016-03-15

    The application of controlled release nutrient (CRN) materials to permeable reactive barriers to promote biodegradation of petroleum hydrocarbons in groundwater was investigated. The longevity of release, influence of flow velocity and petroleum hydrocarbon concentration on nutrient release was assessed using soluble and ion exchange CRN materials; namely Polyon™ and Zeopro™. Both CRN materials, assessed at 4 °C and 23 °C, demonstrated continuing release of nitrogen, phosphorus and potassium (N-P-K) at 3500 bed volumes passing, with longer timeframes of N-P-K release at 4 °C. Zeopro™-activated carbon mixtures demonstrated depletion of N-P-K prior to 3500 bed volumes passing. Increased flow velocity was shown to lower nutrient concentrations in Polyon™ flow cells while nutrient release from Zeopro™ was largely unchanged. The presence of petroleum hydrocarbons, at 1.08 mmol/L and 3.25 mmol/L toluene, were not shown to alter nutrient release from Polyon™ and Zeopro™ across 14 days. These findings suggest that Polyon™ and Zeopro™ may be suitable CRN materials for application to PRBs in low nutrient environments. PMID:26735866

  15. Wetting mechanisms of gel-based controlled-release fertilizers.

    PubMed

    Shavit, U; Reiss, M; Shaviv, A

    2003-02-14

    The release mechanism of gel-based controlled release fertilizers (CRFs) involves water penetration into dry mixtures of fertilizers and gel forming polymers. Water penetration provides an upper limit to the whole release process. Where wetting prediction is often based on models that describe the flow of the liquid phase, vapor motion may become significant when a sharp wetting front exists. In this study we examine the role of vapor and fluid flows in the wetting process of CRFs consisting of urea or KNO(3) mixed with polyacrylamide (PAM). Vapor adsorption isotherms were obtained for typical fertilizer-PAM mixtures. Wetting and release experiments were conducted by dividing the CRFs into regions alternately filled with a pure fertilizer and mixtures of PAM and fertilizer. The experiments were designed in such a way that when the wetting front reaches a mixtures interface, its motion depends on the gradient imposed by the difference in osmotic potential (OP). The coupled equations of vapor and liquid flow in initially dry conditions were solved numerically to demonstrate the conceptual understanding gained by the experiments. The results show that wetting front motion is affected by transport and adsorption of vapor. It was also shown that the release rate is different when wetting is governed by vapor flow or by liquid flow. The release pattern from a multi-regions device was consistent with the wetting pattern, demonstrating the possibility to tailor the release according to periods of peak demand. PMID:12586505

  16. Optically guided controlled release from liposomes with tunable plasmonic nanobubbles.

    PubMed

    Anderson, Lindsey J E; Hansen, Eric; Lukianova-Hleb, Ekaterina Y; Hafner, Jason H; Lapotko, Dmitri O

    2010-06-01

    A new method of optically guided controlled release was experimentally evaluated with liposomes containing a molecular load and gold nanoparticles (NPs). NPs were exposed to short laser pulses to induce transient vapor bubbles around the NPs, plasmonic nanobubbles, in order to disrupt the liposome and eject its molecular contents. The release efficacy was tuned by varying the lifetime and size of the nanobubble with the fluence of the laser pulse. Optical scattering by nanobubbles correlated to the molecular release and was used to guide the release. The release of two fluorescent proteins from individual liposomes has been directly monitored by fluorescence microscopy, while the generation of the plasmonic nanobubbles was imaged and measured with optical scattering techniques. Plasmonic nanobubble-induced release was found to be a mechanical, nonthermal process that requires a single laser pulse and ejects the liposome contents within a millisecond timescale without damage to the molecular cargo and that can be controlled through the fluence of laser pulse. PMID:20156498

  17. Optically Guided Controlled Release from Liposomes With Tunable Plasmonic Nanobubbles

    PubMed Central

    Anderson, Lindsey; Hansen, Eric; Lukianova-Hleb, Ekaterina Y.; Hafner, Jason H.; Lapotko, Dmitri O.

    2010-01-01

    A new method of optically guided controlled release was experimentally evaluated with liposomes containing a molecular load and gold nanoparticles (NPs). NPs were exposed to short laser pulses to induce transient vapor bubbles around the NPs, plasmonic nanobubbles, in order to disrupt the liposome and eject its molecular contents. The release efficacy was tuned by varying the lifetime and size of the nanobubble with the fluence of the laser pulse. Optical scattering by nanobubbles correlated to the molecular release and was used to guide the release. The release of two fluorescent proteins from individual liposomes has been directly monitored by fluorescence microscopy, while the generation of the plasmonic nanobubbles was imaged and measured with optical scattering techniques. Plasmonic nanobubble-induced release was found to be a mechanical, nonthermal process that requires a single laser pulse and ejects of the liposome contents within a millisecond timescale without damage to the molecular cargo and that can be controlled through the fluence of laser pulse. PMID:20156498

  18. Method and apparatus for controlling accidental releases of tritium

    DOEpatents

    Galloway, Terry R. [Berkeley, CA

    1980-04-01

    An improvement in a tritium control system based on a catalytic oxidation reactor wherein accidental releases of tritium into room air are controlled by flooding the catalytic oxidation reactor with hydrogen when the tritium concentration in the room air exceeds a specified limit. The sudden flooding with hydrogen heats the catalyst to a high temperature within seconds, thereby greatly increasing the catalytic oxidation rate of tritium to tritiated water vapor. Thus, the catalyst is heated only when needed. In addition to the heating effect, the hydrogen flow also swamps the tritium and further reduces the tritium release.

  19. Method and apparatus for controlling accidental releases of tritium

    DOEpatents

    Galloway, T.R.

    1980-04-01

    An improvement is described in a tritium control system based on a catalytic oxidation reactor wherein accidental releases of tritium into room air are controlled by flooding the catalytic oxidation reactor with hydrogen when the tritium concentration in the room air exceeds a specified limit. The sudden flooding with hydrogen heats the catalyst to a high temperature within seconds, thereby greatly increasing the catalytic oxidation rate of tritium to tritiated water vapor. Thus, the catalyst is heated only when needed. In addition to the heating effect, the hydrogen flow also swamps the tritium and further reduces the tritium release. 1 fig.

  20. The control of calcium release in heart muscle.

    PubMed

    Cannell, M B; Cheng, H; Lederer, W J

    1995-05-19

    The control of calcium release from intracellular stores (the sarcoplasmic reticulum) in cardiac muscle was examined with the use of a confocal microscope and voltage clamp techniques. Depolarization evoked graded calcium release by altering the extent of spatial and temporal summation of elementary calcium release events called "calcium sparks." These evoked sparks were triggered by local L-type calcium channel currents in a stochastic manner, were similar at different potentials, and resembled spontaneous calcium sparks. Once triggered, the calcium release from the sarcoplasmic reticulum during a calcium spark was independent of the duration of the triggering calcium influx. These results were used to develop a unifying model for cardiac excitation-contraction coupling that explains the large (but paradoxically stable) amplification of the trigger calcium influx by a combination of digital and analog behavior. PMID:7754384

  1. Application of cellulose acetate for controlled release of thymol.

    PubMed

    Milovanovic, Stoja; Markovic, Darka; Aksentijevic, Ksenija; Stojanovic, Dusica B; Ivanovic, Jasna; Zizovic, Irena

    2016-08-20

    Cellulose acetate (CA) was investigated as a carrier towards development of material with controlled release of thymol as a natural substance with strong antibacterial properties using high pressure techniques. Effect of thymol content on CA was confirmed by SEM, FTIR and DSC methods. Kinetic of thymol release from CA was tested using simulated gastric and intestinal fluids (hydrochloric acid and phosphate buffer saline). Results were correlated with Korsmeyer-Peppas and Weibull model. Depending on the thymol content and chemical nature of the release medium, the time of thymol release varied from one to three days indicating CA as a promising carrier of thymol with potential uses from medicine to agriculture. The impregnated CA showed antibacterial activity against 23 tested bacterial strains including methicillin-resistant Staphylococcus aureus (MRSA) which is particularly important bearing in mind that this strain causes fatal infections in humans and animals. PMID:27178940

  2. Advances in mechanistic understanding of release rate control mechanisms of extended-release hydrophilic matrix tablets.

    PubMed

    Timmins, Peter; Desai, Divyakant; Chen, Wei; Wray, Patrick; Brown, Jonathan; Hanley, Sarah

    2016-08-01

    Approaches to characterizing and developing understanding around the mechanisms that control the release of drugs from hydrophilic matrix tablets are reviewed. While historical context is provided and direct physical characterization methods are described, recent advances including the role of percolation thresholds, the application on magnetic resonance and other spectroscopic imaging techniques are considered. The influence of polymer and dosage form characteristics are reviewed. The utility of mathematical modeling is described. Finally, how all the information derived from applying the developed mechanistic understanding from all of these tools can be brought together to develop a robust and reliable hydrophilic matrix extended-release tablet formulation is proposed. PMID:27444495

  3. Motor control differs for increasing and releasing force.

    PubMed

    Park, Seoung Hoon; Kwon, MinHyuk; Solis, Danielle; Lodha, Neha; Christou, Evangelos A

    2016-06-01

    Control of the motor output depends on our ability to precisely increase and release force. However, the influence of aging on force increase and release remains unknown. The purpose of this study, therefore, was to determine whether force control differs while increasing and releasing force in young and older adults. Sixteen young adults (22.5 ± 4 yr, 8 females) and 16 older adults (75.7 ± 6.4 yr, 8 females) increased and released force at a constant rate (10% maximum voluntary contraction force/s) during an ankle dorsiflexion isometric task. We recorded the force output and multiple motor unit activity from the tibialis anterior (TA) muscle and quantified the following outcomes: 1) variability of force using the SD of force; 2) mean discharge rate and variability of discharge rate of multiple motor units; and 3) power spectrum of the multiple motor units from 0-4, 4-10, 10-35, and 35-60 Hz. Participants exhibited greater force variability while releasing force, independent of age (P < 0.001). Increased force variability during force release was associated with decreased modulation of multiple motor units from 35 to 60 Hz (R(2) = 0.38). Modulation of multiple motor units from 35 to 60 Hz was further correlated to the change in mean discharge rate of multiple motor units (r = 0.66) and modulation from 0 to 4 Hz (r = -0.64). In conclusion, these findings suggest that force control is altered while releasing due to an altered modulation of the motor units. PMID:26961104

  4. Controlled release of dual drugs from emulsion electrospun nanofibrous mats.

    PubMed

    Yan, Su; Xiaoqiang, Li; Shuiping, Liu; Xiumei, Mo; Ramakrishna, Seeram

    2009-10-15

    The purpose of this work is to develop a novel type of tissue engineering scaffold or drugs delivery carrier with the capability of encapsulation and controlled release drugs. In this study, Rhodamine B and Bovine Serum Albumin (BSA) were successfully incorporated into nanofibers by means of emulsion electrospinning. The morphology of composite nanofibers was studied by Scanning Electron Microscopy (SEM). The composite nanofibrous mats made from emulsion electrospinning were characterized by water contact angle measurement and X-ray diffraction. In vitro dual drugs release behaviors from composite nanofibrous mats were investigated. The results indicated that the incorporated drug and/or proteins in composite fibrous mats made from electrospinning could be control released by adjusting the processes of emulsions preparation. PMID:19586756

  5. Magnetic Compression of Polyelectrolyte Microcapsules for Controlled Release.

    PubMed

    Hu, Yanan; Liu, Chuanyong; Li, Dongzhi; Long, Yue; Song, Kai; Tung, Chen-Ho

    2015-10-20

    In this study, microcapsules with a magnetic particle as the core and polyelectrolyte multilayers as the shell were fabricated. The cavity of the microcapsules was created by etching the SiO2 layer, which was first coated on the magnetic core particle, and the size of the cavity can be adjusted by the thickness of the SiO2 layer. This magnetically responsive microcapsule deforms upon application of a constant magnetic field and results in the release of the core content, and the release velocity could be controlled by the strength of the magnetic field. This release mechanism is proactive and repeatable, combined with its localized and remote controllability; it can be a powerful tool for delivering medical agents on site. PMID:26402037

  6. Use of controlled release herbicides in waste burial sites

    SciTech Connect

    Burton, F.G.; Cataldo, D.A.; Cline, J.F.; Skiens, W.E.

    1981-07-01

    Controlled-release formulations of herbicides have been applied to the soil in the manner traditional for herbicides: on the surface or mixed into the top few inches of soil. The controlled-release formulation allows another option that we propose to use: to place herbicides, contained in controlled-release formulations, in a layer at least a foot below the surface of the soil, in order to prevent root penetration below that level. Ideally, the herbicide will prevent root tip cell division but will not translocate within the plant, thus assuring that the plant will survive, preserving the ground cover. Trifluralin is one of the herbicides which does not translocate and was chosen for use in this study. A number of applications for this technology are possible; particularly in waste management. In the present studies, we used two different forms of polymeric carrier/delivery (PCD) systems to investigate the controlled release of herbicides. In the initial study, a sheet was made of homogeneous mixtures of an individual polymer and trifluralin. We made several of these sheets, using a different polymer each time (with trifluralin) to compare release rates from the various polymers. We also fabricated cylindrical pellets in two sizes from mixtures of Profax/sup a/ PS-1600 polypropylene and trifluralin, formulated to determine the interaction of PCD systems with soil. Also developed is a trifluralin-releasing device with a theoretical effective lifetime approaching 100 years. The system was designed specifically to protect the asphalt layer or clay/aggregate barriers on uranium mill tailings piles. PCD devices composed of pellets could also be implanted over burial sites for radioactive and/or toxic materials, preventing translocation of those materials to plant shoots, and thence into the biosphere.

  7. Molecular Mechanisms Underlying the Enhanced Analgesic Effect of Oxycodone Compared to Morphine in Chemotherapy-Induced Neuropathic Pain

    PubMed Central

    Thibault, Karine; Calvino, Bernard; Rivals, Isabelle; Marchand, Fabien; Dubacq, Sophie; McMahon, Stephen B.; Pezet, Sophie

    2014-01-01

    Oxycodone is a μ-opioid receptor agonist, used for the treatment of a large variety of painful disorders. Several studies have reported that oxycodone is a more potent pain reliever than morphine, and that it improves the quality of life of patients. However, the neurobiological mechanisms underlying the therapeutic action of these two opioids are only partially understood. The aim of this study was to define the molecular changes underlying the long-lasting analgesic effects of oxycodone and morphine in an animal model of peripheral neuropathy induced by a chemotherapic agent, vincristine. Using a behavioural approach, we show that oxycodone maintains an optimal analgesic effect after chronic treatment, whereas the effect of morphine dies down. In addition, using DNA microarray technology on dorsal root ganglia, we provide evidence that the long-term analgesic effect of oxycodone is due to an up-regulation in GABAB receptor expression in sensory neurons. These receptors are transported to their central terminals within the dorsal horn, and subsequently reinforce a presynaptic inhibition, since only the long-lasting (and not acute) anti-hyperalgesic effect of oxycodone was abolished by intrathecal administration of a GABAB receptor antagonist; in contrast, the morphine effect was unaffected. Our study demonstrates that the GABAB receptor is functionally required for the alleviating effect of oxycodone in neuropathic pain condition, thus providing new insight into the molecular mechanisms underlying the sustained analgesic action of oxycodone. PMID:24618941

  8. Molecular mechanisms underlying the enhanced analgesic effect of oxycodone compared to morphine in chemotherapy-induced neuropathic pain.

    PubMed

    Thibault, Karine; Calvino, Bernard; Rivals, Isabelle; Marchand, Fabien; Dubacq, Sophie; McMahon, Stephen B; Pezet, Sophie

    2014-01-01

    Oxycodone is a μ-opioid receptor agonist, used for the treatment of a large variety of painful disorders. Several studies have reported that oxycodone is a more potent pain reliever than morphine, and that it improves the quality of life of patients. However, the neurobiological mechanisms underlying the therapeutic action of these two opioids are only partially understood. The aim of this study was to define the molecular changes underlying the long-lasting analgesic effects of oxycodone and morphine in an animal model of peripheral neuropathy induced by a chemotherapic agent, vincristine. Using a behavioural approach, we show that oxycodone maintains an optimal analgesic effect after chronic treatment, whereas the effect of morphine dies down. In addition, using DNA microarray technology on dorsal root ganglia, we provide evidence that the long-term analgesic effect of oxycodone is due to an up-regulation in GABAB receptor expression in sensory neurons. These receptors are transported to their central terminals within the dorsal horn, and subsequently reinforce a presynaptic inhibition, since only the long-lasting (and not acute) anti-hyperalgesic effect of oxycodone was abolished by intrathecal administration of a GABAB receptor antagonist; in contrast, the morphine effect was unaffected. Our study demonstrates that the GABAB receptor is functionally required for the alleviating effect of oxycodone in neuropathic pain condition, thus providing new insight into the molecular mechanisms underlying the sustained analgesic action of oxycodone. PMID:24618941

  9. 28 CFR 541.68 - Release from controlled housing status.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Release from controlled housing status. 541.68 Section 541.68 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE INSTITUTIONAL MANAGEMENT INMATE DISCIPLINE AND SPECIAL HOUSING UNITS Procedures for Handling of HIV Positive Inmates...

  10. 28 CFR 541.68 - Release from controlled housing status.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Release from controlled housing status. 541.68 Section 541.68 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE INSTITUTIONAL MANAGEMENT INMATE DISCIPLINE AND SPECIAL HOUSING UNITS Procedures for Handling of HIV Positive Inmates...

  11. 28 CFR 541.68 - Release from controlled housing status.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Release from controlled housing status. 541.68 Section 541.68 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE INSTITUTIONAL MANAGEMENT INMATE DISCIPLINE AND SPECIAL HOUSING UNITS Procedures for Handling of HIV Positive Inmates...

  12. 28 CFR 541.68 - Release from controlled housing status.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Release from controlled housing status. 541.68 Section 541.68 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE INSTITUTIONAL MANAGEMENT INMATE DISCIPLINE AND SPECIAL HOUSING UNITS Procedures for Handling of HIV Positive Inmates...

  13. 28 CFR 541.68 - Release from controlled housing status.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Release from controlled housing status. 541.68 Section 541.68 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE INSTITUTIONAL MANAGEMENT INMATE DISCIPLINE AND SPECIAL HOUSING UNITS Procedures for Handling of HIV Positive Inmates...

  14. CONTROLLED RELEASE, BLIND TEST OF DNAPL REMEDIATION BY ETHANOL FLUSHING

    EPA Science Inventory

    A dense nonaqueous phase liquid (DNAPL) source zone was established within a sheet-pile
    isolated cell through a controlled release of perchloroethylene (PCE) to evaluate DNAPL
    remediation by in-situ cosolvent flushing. Ethanol was used as the cosolvent, and the main remedia...

  15. Biopolymers in controlled release devices for agricultural applications.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The use of biopolymers such as starch for agricultural applications including controlled release devices is growing due the environmental benefits. Recently, concerns have grown about the worldwide spread of parasitic mites (Varroa destructor) that infect colonies of honey bees (Apis mellifera L.). ...

  16. Using Randomized Controlled Trials to Evaluate Interventions for Releasing Prisoners

    ERIC Educational Resources Information Center

    Pettus-Davis, Carrie; Howard, Matthew Owen; Dunnigan, Allison; Scheyett, Anna M.; Roberts-Lewis, Amelia

    2016-01-01

    Randomized controlled trials (RCTs) are rarely used to evaluate social and behavioral interventions designed for releasing prisoners. Objective: We use a pilot RCT of a social support intervention (Support Matters) as a case example to discuss obstacles and strategies for conducting RCT intervention evaluations that span prison and community…

  17. Separate and combined psychopharmacological effects of alprazolam and oxycodone in healthy volunteers

    PubMed Central

    Zacny, James P.; Paice, Judith A.; Coalson, Dennis W.

    2013-01-01

    Background There are epidemiological data indicating that medical and/or nonmedical use of prescription opioids oftentimes involves concurrent use of other substances. One of those substances is benzodiazepines. It would be of relevance to characterize the effects of an opioid and a benzodiazepine when taken together to determine if measures related to abuse liability-related effects and psychomotor performance impairment are increased compared to when the drugs are taken alone. Methods Twenty volunteers participated in a crossover, randomized, double-blind study in which they received placebo, 0.5 mg alprazolam, 10mg oxycodone, and 0.5 mg alprazolam combined with 10mg oxycodone, all p.o. Subjective, psychomotor, and physiological measures were assessed during each of the four sessions. Results Oxycodone by itself increased drug liking and “take again” ratings relative to placebo, but these ratings were not increased when oxycodone was taken with alprazolam, which by itself did not increase either of these ratings. The two drugs in combination produced stronger effects (larger in magnitude or longer lasting) than when either was taken alone on a number of measures, including psychomotor performance impairment. Conclusions In healthy volunteers, abuse liability-related subjective effects of oxycodone were not enhanced by alprazolam. There was enhanced behavioral toxicity when the drugs were taken together, and thus, this is of significant concern from a public safety standpoint. PMID:22365897

  18. Thermosensitive liposomes entrapping iron oxide nanoparticles for controllable drug release.

    PubMed

    Tai, Lin-Ai; Tsai, Pi-Ju; Wang, Yu-Chao; Wang, Yu-Jing; Lo, Leu-Wei; Yang, Chung-Shi

    2009-04-01

    Iron oxide nanoparticles can serve as a heating source upon alternative magnetic field (AMF) exposure. Iron oxide nanoparticles can be mixed with thermosensitive nanovehicles for hyperthermia-induced drug release, yet such a design and mechanism may not be suitable for controllable drug release applications in which the tissues are susceptible to environmental temperature change such as brain tissue. In the present study, iron oxide nanoparticles were entrapped inside of thermosensitive liposomes for AMF-induced drug release while the environmental temperature was maintained at a constant level. Carboxyfluorescein was co-entrapped with the iron oxide nanoparticles in the liposomes as a model compound for monitoring drug release and environmental temperature was maintained with a water circulator jacket. These experiments have been successfully performed in solution, in phantom and in anesthetized animals. Furthermore, the thermosensitive liposomes were administered into rat forearm skeletal muscle, and the release of carboxylfluorescein triggered by the external alternative magnetic field was monitored by an implanted microdialysis perfusion probe with an on-line laser-induced fluorescence detector. In the future such a device could be applied to simultaneous magnetic resonance imaging and non-invasive drug release in temperature-sensitive applications. PMID:19420485

  19. Controlled release tablet formulation containing natural Δ(9)-tetrahydrocannabinol.

    PubMed

    Punyamurthula, Nagendra S; Hingorani, Tushar; Adelli, Goutham; Gul, Waseem; ElSohly, Mahmoud A; Repka, Michael A; Majumdar, Soumyajit

    2016-07-01

    Cannabinoids are increasingly being used in the treatment of chemotherapy-induced nausea and vomiting (CINV) because of their action on the cannabinoid receptors, CB1 and CB2. The currently marketed capsule formulations (sesame oil based and crystalline powder) are required to be administered frequently to maintain therapeutic levels, which leads to non-compliance. In the present study, oral controlled release tablet formulations of Δ(9)-tetrahydrocannabinol (THC) were prepared using the lipids Precirol® and Compritol®. Release profiles using THC-lipid matrices and/or with the lipids in the external phase (blend) were evaluated. The effect of directly compressible diluents lactose mixture (Ludipress®), dicalcium phosphate anhydrous (Emcompress®) and microcrystalline cellulose (Avicel® 102) on tablet characteristics and in vitro drug release was also investigated. Further, in vitro THC release in the presence of a lipase inhibitor, Pluronic® F68, was also studied. A 24 h zero-order THC release profile was obtained with a combination of Precirol® and Compritol® in the compression blend. Addition of Pluronic® F68 did not alter THC release in vitro. These optimized tablets were chemically and physically stable for 3 months, the last time point tested, at 25 °C/60% RH. The overall results demonstrate the feasibility of preparing oral THC tablets for once a day administration which can improve CINV management. PMID:26585693

  20. Controlled-release scale inhibitor for use in fracturing treatments

    SciTech Connect

    Powell, R.J.; Gdanski, R.D.; McCabe, M.A.; Buster, D.C.

    1995-11-01

    This paper describes results of laboratory and field testing of a solid, controlled-release scale inhibitor for use in fracturing treatments. Laboratory testing with a continuous flow apparatus has yielded inhibitor release rates under dynamic conditions. The inhibitor was tested to determine the minimum inhibitor concentration required to inhibit the formation of CaCO{sub 3}, CaSO{sub 4}, and BaSO{sub 4} scales in a brine. A model to predict the long-term release rate of the inhibitor was developed from data collected on the continuous flow apparatus. Data from treated wells will be compared with predictions of the model. Inhibitor release-rate testing in a continuous-flow apparatus shows that a solid, calcium-magnesium polyphosphate inhibitor has a sustained release profile. Release-rate testing shows that the inhibitor can be used up to 175 F. The inhibitor is compatible with both borate and zirconium crosslinked fracturing fluids and foamed fluids. The effective lifetime of the scale treatment can be predicted based on a model developed from laboratory data. The input variables required for the prediction include: temperature, water production, amount of inhibitor, minimum effective concentration of inhibitor for the specific brine. The model can be used to aid in the design of the scale inhibitor treatment.

  1. Controlled release of alendronate from nitrogen-doped mesoporous carbon

    DOE PAGESBeta

    Saha, Dipendu; Spurri, Amanda; Chen, Jihua; Hensley, Dale K.

    2016-04-13

    With this study, we have synthesized a nitrogen doped mesoporous carbon with the BET surface area of 1066 m2/g, total pore volume 0.6 cm3/g and nitrogen content of 0.5%. Total alendronate adsorption in this carbon was ~5%. The release experiments were designed in four different media with sequential pH values of 1.2, 4.5, 6.8 and 7.4 for 3, 1, 3 and 5 h, respectively and at 37 °C to imitate the physiological conditions of stomach, duodenum, small intestine and colon, respectively. Release of the drug demonstrated a controlled fashion; only 20% of the drug was released in the media withmore » pH = 1.2, whereas 64% of the drug was released in pH = 7.4. This is in contrary to pure alendronate that was completely dissolved within 30 min in the first release media (pH = 1.2) only. The relatively larger uptake of alendronate in this carbon and its sustained fashion of release can be attributed to the hydrogen bonding between the drug and the nitrogen functionalities on carbon surface. Based on this result, it can be inferred that this formulation may lower the side effects of oral delivery of alendronate.« less

  2. Controlled release of ethylene via polymeric films for food packaging

    NASA Astrophysics Data System (ADS)

    Pisano, Roberto; Bazzano, Marco; Capozzi, Luigi Carlo; Ferri, Ada; Sangermano, Marco

    2015-12-01

    In modern fruit supply chain a common method to trigger ripening is to keep fruits inside special chambers and initiate the ripening process through administration of ethylene. Ethylene is usually administered through cylinders with inadequate control of its final concentration in the chamber. The aim of this study is the development of a new technology to accurately regulate ethylene concentration in the atmosphere where fruits are preserved: a polymeric film, containing an inclusion complex of α-cyclodextrin with ethylene, was developed. The complex was prepared by molecular encapsulation which allows the entrapment of ethylene into the cavity of α-cyclodextrin. After encapsulation, ethylene can be gradually released from the inclusion complex and its release rate can be regulated by temperature and humidity. The inclusion complex was dispersed into a thin polymeric film produced by UV-curing. This method was used because is solvent-free and involves low operating temperature; both conditions are necessary to prevent rapid release of ethylene from the film. The polymeric films were characterized with respect to thermal behaviour, crystalline structure and kinetics of ethylene release, showing that can effectively control the release of ethylene within confined volume.

  3. Controlled release of growth factors for regenerative medicine.

    PubMed

    Liu, Libiao; Zhou, Xinwei; Xu, Yufan; Zhang, Weiming; Liu, Cheng-Hsien; Wang, Xiaohong

    2015-01-01

    How to release growth factors (GFs) scientifically to promote stem cell proliferation and differentiation is one of the most significant research focuses in the field of regenerative medicine. In a controlled release system, growth factors, extracellular matrices or biomaterial carriers, and sometimes stem cells together form a geometric entirety. Biomaterial carriers provide GFs with a support structure to be adhered, immobilized, encapsulated or/and protected. As a unity, the release rate and rhythm of GFs on cells are normally very delicate and precise. Up to now, the best strategy for clinical applications is the combination systems that encapsulate GFs in microspheres, particularly the nano- or micro-encapsulation techniques integrated GFs with biomaterial carriers. In this mini review, we summarize the current progress in GF delivery systems for regenerative medicine and provide an outlook on two main aspects: one is the classes of stem cells and GFs that have been used frequently in regenerative medicine, including their respective application conditions and functions; the other is the controlled GF release systems, in which various GFs are released orderly and continuously without diffusing simply and rapidly, including their respective opportunities and challenges. PMID:25594403

  4. Use of polysulfone in controlled-release NPK fertilizer formulations.

    PubMed

    Tomaszewska, Maria; Jarosiewicz, Anna

    2002-07-31

    Encapsulation of fertilizers in polymeric coatings is a method used to reduce fertilizer losses and to minimize environmental pollution. Polysulfone was used for a coating preparation for soluble NPK granular fertilizer in controlled-release fertilizer formulations. The coatings were formed by the phase inversion technique (wet method). The influence of the polymer concentration in the film-forming solution on the physical properties of the coatings was examined. The coating structure controls the diffusion of the elements from the interior of the fertilizer granule. It was experimentally confirmed that the use of polysulfone as a coating for a soluble fertilizer decreases the release rate of components. Moreover, the release rate of nutrients from coated granules decreases with the decrease of the coating porosity. In the case of coating with 38.5% porosity, prepared from 13.5% polymer solution after 5 h of test, 100% of NH(4)(+) was released, whereas only 19.0% of NH(4)(+) was released after 5 h for the coating with 11% porosity. In addition, coating of fertilizers leads to improvement of handling properties, and the crushing strength of all coated fertilizers was an average 40% higher than that for uncoated NPK fertilizer. PMID:12137488

  5. Controlled release of molecular components of dendrimer/bioactive complexes

    DOEpatents

    Segalman, Daniel J.; Wallace, J. Shield

    1998-01-01

    A method for releasing molecules (guest molecules) from the matrix formed by the structure of another molecule (host molecule) in a controllable manner has been invented. This method has many applications in science and industry. In addition, applications based on such molecular systems may revolutionize significant areas of medicine, in particular the treatment of cancer and of viral infection. Similar effects can also be obtained by controlled fragmentation of a source molecule, where the molecular fragments form the active principle.

  6. Controlled release of molecular components of dendrimer/bioactive complexes

    DOEpatents

    Segalman, D.J.; Wallace, J.S.

    1998-08-18

    A method for releasing molecules (guest molecules) from the matrix formed by the structure of another molecule (host molecule) in a controllable manner has been invented. This method has many applications in science and industry. In addition, applications based on such molecular systems may revolutionize significant areas of medicine, in particular the treatment of cancer and of viral infection. Similar effects can also be obtained by controlled fragmentation of a source molecule, where the molecular fragments form the active principle. 13 figs.

  7. Photocatalytic Degradation of Cell Membrane Coatings for Controlled Drug Release.

    PubMed

    Rao, Lang; Meng, Qian-Fang; Huang, Qinqin; Liu, Pei; Bu, Lin-Lin; Kondamareddy, Kiran Kumar; Guo, Shi-Shang; Liu, Wei; Zhao, Xing-Zhong

    2016-06-01

    Biomimetic cell-membrane-camouflaged particles with desirable features have been widely used for various biomedical applications. However, there are few reports on employing these particles for cancer drug delivery due to the failure of the membrane coatings to be efficiently degraded in the tumor microenvironment which hampers the drug release. In this work, core-shell SiO2 @TiO2 nanoparticles with enhanced photocatalytic activity are used for controlled degradation of surface erythrocyte membrane coatings. The antitumor drug docetaxel is encapsulated into nanocarriers to demonstrate the controlled drug release under ultraviolet irradiation, and the drug-loaded nanoparticles are further used for enhanced cancer cell therapy. Here, a simple but practical method for degradation of cell membrane coatings is presented, and a good feasibility of using cell membrane-coated nanocarriers for controlled drug delivery is demonstrated. PMID:27191802

  8. Electrospun cellular microenvironments: Understanding controlled release and scaffold structure.

    PubMed

    Szentivanyi, Andreas; Chakradeo, Tanmay; Zernetsch, Holger; Glasmacher, Birgit

    2011-04-30

    Electrospinning is a versatile technique in tissue engineering for the production of scaffolds. To guide tissue development, scaffolds must provide specific biochemical, structural and mechanical cues to cells and deliver them in a controlled fashion over time. Electrospun scaffold design thus includes aspects of both controlled release and structural cues. Controlled multicomponent and multiphasic drug delivery can be achieved by the careful application and combination of novel electrospinning techniques, i.e., emulsion and co-axial electrospinning. Drug distribution and polymer properties influence the resulting release kinetics. Pore size is far more relevant as a structural parameter than previously recognized. It enables cell proliferation and ingrowth, whereas fiber diameter predominantly influences cell fate. Both parameters can be exploited by combining multiple fiber types in the form of multifiber and multilayer scaffolds. Such scaffolds are required to reproduce more complex tissue structures. PMID:21145932

  9. Controlled release mechanisms of spontaneously forming unilamellar vesicles.

    PubMed

    Nieh, Mu-Ping; Katsaras, John; Qi, Xiaoyang

    2008-06-01

    Spontaneously forming small unilamellar vesicles (SULVs) are easy to prepare and show great promise for use in delivering therapeutic payloads. We report of SULVs made up of the ternary phospholipid mixture, dimyristoyl-phosphatidylcholine (DMPC), dihexanoyl-phosphatidylcholine (DHPC) and dimyristoyl-phosphatidylglycerol (DMPG), which have been characterized by small angle neutron scattering (SANS). These low-polydispersity (0.14-0.19) SULVs range in size (i.e., radius) from 110 to 215 A and are capable of entrapping, and subsequently releasing, hydrophilic molecules (e.g., fluorescent dyes and quenchers) in a controlled fashion over two different temperature ranges. The low-temperature release mechanism involves the SULVs transforming into discoidal micelles, with an onset temperature (T(o)) of ~32 degrees C, while the high-temperature release mechanism is more gradual, presumably the result of defects formed through the continuous dissolution of DHPC into solution. Both of these mechanisms differ from other, previously reported thermosensitive liposomes. PMID:18394425

  10. Carbon monoxide – physiology, detection and controlled release

    PubMed Central

    Heinemann, Stefan H.; Hoshi, Toshinori; Westerhausen, Matthias

    2014-01-01

    Carbon monoxide (CO) is increasingly recognized as a cell-signalling molecule akin to nitric oxide (NO). CO has attracted particular attention as a potential therapeutic agent because of its reported anti-hypertensive, anti-inflammatory and cell-protective effects. We discuss recent progress in identifying new effector systems and elucidating the mechanisms of action of CO on, e.g., ion channels, as well as the design of novel methods to monitor CO in cellular environments. We also report on recent developments in the area of CO-releasing molecules (CORMs) and materials for controlled CO application. Novel triggers for CO release, metal carbonyls and degradation mechanisms of CORMs, are highlighted. In addition, potential formulations of CORMs for targeted CO release are discussed. PMID:24556640

  11. Optogenetic Control of Serotonin and Dopamine Release in Drosophila Larvae

    PubMed Central

    2014-01-01

    Optogenetic control of neurotransmitter release is an elegant method to investigate neurobiological mechanisms with millisecond precision and cell type-specific resolution. Channelrhodopsin-2 (ChR2) can be expressed in specific neurons, and blue light used to activate those neurons. Previously, in Drosophila, neurotransmitter release and uptake have been studied after continuous optical illumination. In this study, we investigated the effects of pulsed optical stimulation trains on serotonin or dopamine release in larval ventral nerve cords. In larvae with ChR2 expressed in serotonergic neurons, low-frequency stimulations produced a distinct, steady-state response while high-frequency patterns were peak shaped. Evoked serotonin release increased with increasing stimulation frequency and then plateaued. The steady-state response and the frequency dependence disappeared after administering the uptake inhibitor fluoxetine, indicating that uptake plays a significant role in regulating the extracellular serotonin concentration. Pulsed stimulations were also used to evoke dopamine release in flies expressing ChR2 in dopaminergic neurons and similar frequency dependence was observed. Release due to pulsed optical stimulations was modeled to determine the uptake kinetics. For serotonin, Vmax was 0.54 ± 0.07 μM/s and Km was 0.61 ± 0.04 μM; and for dopamine, Vmax was 0.12 ± 0.03 μM/s and Km was 0.45 ± 0.13 μM. The amount of serotonin released per stimulation pulse was 4.4 ± 1.0 nM, and the amount of dopamine was 1.6 ± 0.3 nM. Thus, pulsed optical stimulations can be used to mimic neuronal firing patterns and will allow Drosophila to be used as a model system for studying mechanisms underlying neurotransmission. PMID:24849718

  12. Sustainable practices for fertilizer use through controlled release techniques

    NASA Astrophysics Data System (ADS)

    Faez, Roselena; Messa, Lucas; Froes, José; Souza, Claudinei

    2015-04-01

    Controlled release fertilizers are efficient tools that increase the sustainability of agricultural practices. However, the biodegradability of the matrices and the determination of the release into soil still require some investigation. This work describes the preparation of potassium-containing microspheres based on chitosan- montmorillonite clay as fertilizer double coated. The release profile in water (ion conductivity measurement) and soil (ion movement performed with time-domain reflectometry (TDR) technique) were evaluated. The potassium-containing microspheres were placed in a 7.5-L container filled with soil (Typic dystrophic LVd). The container was prepared with a water drainage system consisting of a thin layer of gravel at the bottom, which was followed by a geotextile fabric to prevent the loss of soil. The container was filled with soil (9 kg) in layers of 0.05 m to simulate the original bulk density of 1.30 g.cm-3. Each container received 4 g of microspheres placed at a single spot. They were placed at a depth of 10 cm. The fertilizer release was monitored using three electromagnetic probes for TDR that consisted of three continuous metal rods of 20 cm, which were in contact with the material and can be used to estimate the moisture and electrical conductivity. One probe was installed at the center of the container, which meant the rod was in contact with the microspheres in the soil. The other two probes were installed 5 cm from the central probe, and they were only in contact with the soil. Therefore, the purpose of these probes was to monitor the lateral displacement of the fertilizer from the microspheres in the soil. The release in water is fast than in soil, since the total amount of fertilizer in water was delivery during only one week and in soil during 60 days the fertilizer still continue drifting. The composite based on chitosan biopolymer as controlled release material is an efficient method to monitor the fertilizer consumption.

  13. Cellulose, Chitosan, and Keratin Composite Materials. Controlled Drug Release

    PubMed Central

    2015-01-01

    A method was developed in which cellulose (CEL) and/or chitosan (CS) were added to keratin (KER) to enable [CEL/CS+KER] composites to have better mechanical strength and wider utilization. Butylmethylimmidazolium chloride ([BMIm+Cl–]), an ionic liquid, was used as the sole solvent, and because the [BMIm+Cl–] used was recovered, the method is green and recyclable. Fourier transform infrared spectroscopy results confirm that KER, CS, and CEL remain chemically intact in the composites. Tensile strength results expectedly show that adding CEL or CS into KER substantially increases the mechanical strength of the composites. We found that CEL, CS, and KER can encapsulate drugs such as ciprofloxacin (CPX) and then release the drug either as a single or as two- or three-component composites. Interestingly, release rates of CPX by CEL and CS either as a single or as [CEL+CS] composite are faster and independent of concentration of CS and CEL. Conversely, the release rate by KER is much slower, and when incorporated into CEL, CS, or CEL+CS, it substantially slows the rate as well. Furthermore, the reducing rate was found to correlate with the concentration of KER in the composites. KER, a protein, is known to have secondary structure, whereas CEL and CS exist only in random form. This makes KER structurally denser than CEL and CS; hence, KER releases the drug slower than CEL and CS. The results clearly indicate that drug release can be controlled and adjusted at any rate by judiciously selecting the concentration of KER in the composites. Furthermore, the fact that the [CEL+CS+KER] composite has combined properties of its components, namely, superior mechanical strength (CEL), hemostasis and bactericide (CS), and controlled drug release (KER), indicates that this novel composite can be used in ways which hitherto were not possible, e.g., as a high-performance bandage to treat chronic and ulcerous wounds. PMID:25548871

  14. Controlled release niosome embedded chitosan system: effect of crosslink mesh dimensions on drug release.

    PubMed

    Williams, Eva Christabel; Toomey, Ryan; Alcantar, Norma

    2012-12-01

    We report on a model chemotherapy drug delivery system comprising nonionic surfactant vesicles (niosomes) packaged within a temperature-sensitive chitosan network. This smart packaging, or package-within-a package system, provides two distinct advantages. First, the gel prevents circulation of the niosomes and maintains delivery in the vicinity of a tumor. Second, the chitosan network protects the niosomes against fluctuations in tonicity, which affects delivery rates. Tonicity is the sum of the concentrations of the solutes which have the capacity to exert an osmotic force across the membrane. All release rate experiments were conducted with 5,6-carboxyfluorescein, a fluorescent dye. Release rates were monitored from both bare niosomes alone and niosome-embedded, chitosan networks. It was observed that chitosan networks prolonged delivery from 100 h to 55 days in low ionic strength environment and pH conditions similar to a tumor site. The primary effect of chitosan is to add control on release time and dosage, and stabilize the niosomes through a high ionic strength surrounding that prevents uncontrolled bursting of the niosomes. Secondary factors include crosslink density of the chitosan network, molecular weight of the individual chitosan polymers, dye concentration within the niosomes, and the number density of niosomes packaged within the chitosan network. Each of these factors can be altered to fine-tune release rates. PMID:22733611

  15. Oxycodone involvement in drug abuse deaths: a DAWN-based classification scheme applied to an oxycodone postmortem database containing over 1000 cases.

    PubMed

    Cone, Edward J; Fant, Reginald V; Rohay, Jeffrey M; Caplan, Yale H; Ballina, Mayra; Reder, Robert F; Spyker, Daniel; Haddox, J David

    2003-03-01

    An oxycodone postmortem database was created from 1243 solicited cases from Medical Examiner and Coroner (ME/C) offices in 23 states in the United States over the period from August 27, 1999, through January 17, 2002. The request for cases was specific to only those cases in which the ME/C opined that the death involved oxycodone. Each case was evaluated to determine the role of oxycodone and the specific drug product OxyContin tablets in the death. Oxycodone identification was based on toxicology testing, and OxyContin identification was based on evidence found at the scene, credible witness reports, or identification of tablets in gastrointestinal contents. A system of case categorization was developed for this study based on the Drug Abuse Warning Network (DAWN) system for reporting drug abuse mortality data in the United States, using the same standardized, well-understood terminology. Of the 1243 cases, 79 cases were incomplete and could not be evaluated. There were an additional 150 cases submitted in which oxycodone was not identified by the originating ME/C. Of the remaining 1014 cases, 919 (90.6%) were related to drug abuse, whereas 95 (9.4%) cases were categorized as not involving drug abuse. Only 30 (3.3%) of the drug abuse cases involved oxycodone as the single reported chemical entity; of these, 12 cases had OxyContin identified as a source of oxycodone. Of the 919 drug abuse cases, the vast majority (N = 889, 96.7%) were multiple drug abuse deaths in which there was at least one other plausible contributory drug in addition to oxycodone. The most prevalent drug combinations were oxycodone in combination with benzodiazepines, alcohol, cocaine, other narcotics, marijuana, or antidepressants. Using the DAWN definitions, drug abuse cases were further categorized as drug-induced or drug-related. A total of 851 (92.6%) cases met the criteria for classification as being drug-induced, and the remaining 68 (7.4%) cases were categorized as drug-related. Cause

  16. Use of microcapsules as controlled release devices for coatings.

    PubMed

    Andersson Trojer, Markus; Nordstierna, Lars; Bergek, Jonatan; Blanck, Hans; Holmberg, Krister; Nydén, Magnus

    2015-08-01

    Biofouling of surfaces is a considerable problem in many industrial sectors and for the public community in general. The problem is usually approached by the use of functional coatings and most of such antifouling coatings rely on the effect of biocides. However, a substantial drawback is the poor control over the release of the biocide as well as its degradation in the paint. Encapsulation of the biocides in microcapsules is a promising approach that may overcome some of the problems associated with the more traditional ways of incorporating the antifouling agent into the formulation. In this review, we summarize more than a decade of microcapsule research from our lab as well as from other groups working on this topic. Focus will be on two coacervation-based encapsulation techniques; the internal phase separation method and the double emulsion method, which together enable the encapsulation of a broad spectrum of biocides with different physicochemical properties. The release of the biocide from core-shell particles and from encapsulated biocides in coatings is treated in detail. The release behaviour is interpreted in terms of the physicochemical properties of the core-shell particle and the coating matrix. In addition, special attention is given to the experimental release methodology and the implementation of proper diffusion models to describe the release. At the end of the review examples of antifouling properties of some coatings against common biofoulers are presented. PMID:25441449

  17. Highly Efficient Thermoresponsive Nanocomposite for Controlled Release Applications

    PubMed Central

    Yassine, Omar; Zaher, Amir; Li, Er Qiang; Alfadhel, Ahmed; Perez, Jose E.; Kavaldzhiev, Mincho; Contreras, Maria F.; Thoroddsen, Sigurdur T.; Khashab, Niveen M.; Kosel, Jurgen

    2016-01-01

    Highly efficient magnetic release from nanocomposite microparticles is shown, which are made of Poly (N-isopropylacrylamide) hydrogel with embedded iron nanowires. A simple microfluidic technique was adopted to fabricate the microparticles with a high control of the nanowire concentration and in a relatively short time compared to chemical synthesis methods. The thermoresponsive microparticles were used for the remotely triggered release of Rhodamine (B). With a magnetic field of only 1 mT and 20 kHz a drug release of 6.5% and 70% was achieved in the continuous and pulsatile modes, respectively. Those release values are similar to the ones commonly obtained using superparamagnetic beads but accomplished with a magnetic field of five orders of magnitude lower power. The high efficiency is a result of the high remanent magnetization of the nanowires, which produce a large torque when exposed to a magnetic field. This causes the nanowires to vibrate, resulting in friction losses and heating. For comparison, microparticles with superparamagnetic beads were also fabricated and tested; while those worked at 73 mT and 600 kHz, no release was observed at the low field conditions. Cytotoxicity assays showed similar and high cell viability for microparticles with nanowires and beads. PMID:27335342

  18. Highly Efficient Thermoresponsive Nanocomposite for Controlled Release Applications.

    PubMed

    Yassine, Omar; Zaher, Amir; Li, Er Qiang; Alfadhel, Ahmed; Perez, Jose E; Kavaldzhiev, Mincho; Contreras, Maria F; Thoroddsen, Sigurdur T; Khashab, Niveen M; Kosel, Jurgen

    2016-01-01

    Highly efficient magnetic release from nanocomposite microparticles is shown, which are made of Poly (N-isopropylacrylamide) hydrogel with embedded iron nanowires. A simple microfluidic technique was adopted to fabricate the microparticles with a high control of the nanowire concentration and in a relatively short time compared to chemical synthesis methods. The thermoresponsive microparticles were used for the remotely triggered release of Rhodamine (B). With a magnetic field of only 1 mT and 20 kHz a drug release of 6.5% and 70% was achieved in the continuous and pulsatile modes, respectively. Those release values are similar to the ones commonly obtained using superparamagnetic beads but accomplished with a magnetic field of five orders of magnitude lower power. The high efficiency is a result of the high remanent magnetization of the nanowires, which produce a large torque when exposed to a magnetic field. This causes the nanowires to vibrate, resulting in friction losses and heating. For comparison, microparticles with superparamagnetic beads were also fabricated and tested; while those worked at 73 mT and 600 kHz, no release was observed at the low field conditions. Cytotoxicity assays showed similar and high cell viability for microparticles with nanowires and beads. PMID:27335342

  19. Highly Efficient Thermoresponsive Nanocomposite for Controlled Release Applications

    NASA Astrophysics Data System (ADS)

    Yassine, Omar; Zaher, Amir; Li, Er Qiang; Alfadhel, Ahmed; Perez, Jose E.; Kavaldzhiev, Mincho; Contreras, Maria F.; Thoroddsen, Sigurdur T.; Khashab, Niveen M.; Kosel, Jurgen

    2016-06-01

    Highly efficient magnetic release from nanocomposite microparticles is shown, which are made of Poly (N-isopropylacrylamide) hydrogel with embedded iron nanowires. A simple microfluidic technique was adopted to fabricate the microparticles with a high control of the nanowire concentration and in a relatively short time compared to chemical synthesis methods. The thermoresponsive microparticles were used for the remotely triggered release of Rhodamine (B). With a magnetic field of only 1 mT and 20 kHz a drug release of 6.5% and 70% was achieved in the continuous and pulsatile modes, respectively. Those release values are similar to the ones commonly obtained using superparamagnetic beads but accomplished with a magnetic field of five orders of magnitude lower power. The high efficiency is a result of the high remanent magnetization of the nanowires, which produce a large torque when exposed to a magnetic field. This causes the nanowires to vibrate, resulting in friction losses and heating. For comparison, microparticles with superparamagnetic beads were also fabricated and tested; while those worked at 73 mT and 600 kHz, no release was observed at the low field conditions. Cytotoxicity assays showed similar and high cell viability for microparticles with nanowires and beads.

  20. Formulation and Evaluation of Controlled Release Floating Microballoons of Stavudine

    PubMed Central

    Vidyadhara, Suryadevara; Sasidhar, Reddyvalam Lankapalli; Balakrishna, Talamanchi; Balaji, Boyapati; Amrutha, Ravi

    2015-01-01

    The aim of this study was to formulate and evaluate stavudine floating microballoons for controlled drug release. Initially, the drug-loaded low-density granular pellets were prepared with hydroxypropyl methylcellulose E5 grade and by using isopropyl alcohol as a granulating fluid. Further, the low-density granular pellets were subjected to microencapsulation by an emulsion evaporation technique using ethyl cellulose 7 cps and Eudragit S 100 as coating polymers and 1% w/v polyethylene glycol 400 as aqueous phase. The prepared microballoons were characterized for their particle size analysis, angle of repose, and compressibility index. The in vitro release studies were performed in 0.1 N HCl as medium. The prepared microballoons were free-flowing and spherical in shape. From all the formulations, F5E and F5F can be considered as promising controlled release floating microballoons of stavudine providing first-order release over a period of 12 hours, with a minimum floating lag time of 1 minute. It was found that the ratio of the drug & polymer, stirring speed, and concentration of surfactant were the most significant variables which influenced the size of the stavudine microballoons under the applied experimental conditions. PMID:26839847

  1. pH-controlled drug release for dental applications

    NASA Astrophysics Data System (ADS)

    Wironen, John Francis

    A large proportion of the dental fillings replaced at present are revised because of the perceived presence of a recurrent caries under or adjacent to the restoration. Many of these perceived caries may not exist, while others may go undetected. This work describes the preparation of drug loaded polymer microspheres that sense the presence of the bacteria that cause caries by the associated presence of acid by-products of digestion. These microspheres are designed to swell and release their antimicrobial drugs once the pH drops to a level that would normally cause caries. The preparation of the microspheres as well as their loading with potassium fluoride, chlorhexidine digluconate, chlorhexidine dihydrochloride, chlorhexidine diacetate, and tetracycline hydrochloride are described. A detailed study of the controlled release behavior of fluoride as a function of polymer composition and pH is presented first. A study of the release kinetics of potassium fluoride, chlorhexidine digluconate, diacetate, dihydrochloride, and tetracycline hydrochloride as a function of pH in the same polymer system is then presented. Additional studies of the swelling kinetics of chlorhexidine-loaded microspheres in various pH buffers are discussed with special reference to correlations with the controlled-release data. Finally, an experiment in which the microspheres are tested in an in vitro bacteria model that includes Streptococcus mutans is presented and discussed in detail.

  2. Formulation and Evaluation of Controlled Release Floating Microballoons of Stavudine.

    PubMed

    Vidyadhara, Suryadevara; Sasidhar, Reddyvalam Lankapalli; Balakrishna, Talamanchi; Balaji, Boyapati; Amrutha, Ravi

    2015-01-01

    The aim of this study was to formulate and evaluate stavudine floating microballoons for controlled drug release. Initially, the drug-loaded low-density granular pellets were prepared with hydroxypropyl methylcellulose E5 grade and by using isopropyl alcohol as a granulating fluid. Further, the low-density granular pellets were subjected to microencapsulation by an emulsion evaporation technique using ethyl cellulose 7 cps and Eudragit S 100 as coating polymers and 1% w/v polyethylene glycol 400 as aqueous phase. The prepared microballoons were characterized for their particle size analysis, angle of repose, and compressibility index. The in vitro release studies were performed in 0.1 N HCl as medium. The prepared microballoons were free-flowing and spherical in shape. From all the formulations, F5E and F5F can be considered as promising controlled release floating microballoons of stavudine providing first-order release over a period of 12 hours, with a minimum floating lag time of 1 minute. It was found that the ratio of the drug & polymer, stirring speed, and concentration of surfactant were the most significant variables which influenced the size of the stavudine microballoons under the applied experimental conditions. PMID:26839847

  3. Controlled Release of Agrochemicals Intercalated into Montmorillonite Interlayer Space

    PubMed Central

    2014-01-01

    Periodic application of agrochemicals has led to high cost of production and serious environmental pollution. In this study, the ability of montmorillonite (MMT) clay to act as a controlled release carrier for model agrochemical molecules has been investigated. Urea was loaded into MMT by a simple immersion technique while loading of metalaxyl was achieved by a rotary evaporation method. The successful incorporation of the agrochemicals into the interlayer space of MMT was confirmed by several techniques, such as, significant expansion of the interlayer space, reduction of Barrett-Joyner-Halenda (BJH) pore volumes and Brunauer-Emmett-Teller (BET) surface areas, and appearance of urea and metalaxyl characteristic bands on the Fourier-transform infrared spectra of the urea loaded montmorillonite (UMMT) and metalaxyl loaded montmorillonite (RMMT) complexes. Controlled release of the trapped molecules from the matrix was done in water and in the soil. The results reveal slow and sustained release behaviour for UMMT for a period of 10 days in soil. For a period of 30 days, MMT delayed the release of metalaxyl in soil by more than 6 times. It is evident that MMT could be used to improve the efficiency of urea and metalaxyl delivery in the soil. PMID:24696655

  4. Controlled Release for Local Delivery of Drugs: Barriers and Models

    PubMed Central

    Weiser, Jennifer R.; Saltzman, W. Mark

    2014-01-01

    Controlled release systems are an effective means for local drug delivery. In local drug delivery, the major goal is to supply therapeutic levels of a drug agent at a physical site in the body for a prolonged period. A second goal is to reduce systemic toxicities, by avoiding the delivery of agents to non-target tissues remote from the site. Understanding the dynamics of drug transport in the vicinity of a local drug delivery device is helpful in achieving both of these goals. Here, we provide an overview of controlled release systems for local delivery and we review mathematical models of drug transport in tissue, which describe the local penetration of drugs into tissue and illustrate the factors—such as diffusion, convection, and elimination—that control drug dispersion and its ultimate fate. This review highlights the important role of controlled release science in development of reliable methods for local delivery, as well as the barriers to accomplishing effective delivery in the brain, blood vessels, mucosal epithelia, and the skin. PMID:24801251

  5. Diisocyanate mediated polyether modified gelatin drug carrier for controlled release

    PubMed Central

    Vijayakumar, Vediappan; Subramanian, Kaliappagounder

    2013-01-01

    Gelatin is an extensively studied biopolymer hydrogel drug carrier due to its biocompatibility, biodegradability and non-toxicity of its biodegraded products formed in vivo. But with the pristine gelatin it is difficult to achieve a controlled and desirable drug release characteristics due to its structural and thermal lability and high solubility in aqueous biofluids. Hence it is necessary to modify its solubility and structural stability in biofluids to achieve controlled release features with improved drug efficacy and broader carrier applications. In the present explorations an effort is made in this direction by cross linking gelatin to different extents using hitherto not studied isocyanate terminated poly(ether) as a macrocrosslinker prepared from poly(ethylene glycol) and isophorone diisocyanate in dimethyl sulfoxide. The crosslinked samples were analyzed for structure by Fourier transform-infrared spectroscopy, thermal behavior through thermogravimetric analysis and differential scanning calorimetry. The cross linked gelatins were biodegradable, insoluble and swellable in biofluids. They were evaluated as a carrier for in vitro drug delivery taking theophylline as a model drug used in asthma therapy. The crosslinking of gelatin decreased the drug release rate by 10–20% depending upon the extent of crosslinking. The modeled drug release characteristics revealed an anomalous transport mechanism. The release rates for ampicillin sodium, 5-fluorouracil and theophylline drugs in a typical crosslinked gelatin carrier were found to depend on the solubility and hydrophobicity of the drugs, and the pH of the fluid. The observed results indicated that this material can prove its mettle as a viable carrier matrix in drug delivery applications. PMID:24493973

  6. Opioid switch from low dose of oral oxycodone to transdermal fentanyl matrix patch for patients with stable thoracic malignancy-related pain

    PubMed Central

    2014-01-01

    Background The effectiveness and safety of switch from oral oxycodone to fentanyl patch is little known. Here, we investigated if early phase opioid switch from low dose of oral oxycodone to transdermal fentanyl matrix patch provided any benefits for patients with thoracic malignancy and stable cancer-related pain. Methods This open-label two-centered prospective study enrolled patients with thoracic malignancy suffering persistent malignancy-related pain with numeric rating scale of pain intensity ≤ 3 which had been controlled by oral oxycodone ≤ 20 mg/day. Eligible patients switched from oral oxycodone to 12.5 μg/h of transdermal fentanyl matrix patch. The dose was allowed to be titrated upwards every 3 day by 25-50%, except for the first increase from 12.5 μg/hr to 25 μg/hr,until achieving adequate pain control. The data on patients’ global assessment scores measured on a five-step scale, an 11-point numeric rating scale of pain intensity, the severity of adverse effects using a four-point categorical rating scale, and the Epworth sleepiness scale questionnaire were collected for 15 days. Results Forty-nine eligible patients were analyzed. Overall patients’ satisfaction score significantly improved from day 1 (2.7 ± 0.9) to day 15 (2.3 ± 0.9) (p < 0.05), and 90% and 78% of patients remained to receive the minimum dose of fentanyl patch on day 8 and 15 from the opioid switch. There was a significant difference in sleepiness throughout the study period, though no difference was detected in pain intensity and other adverse effects. Conclusion Transdermal fentanyl matrix patch is an alternative analgesic option for a stable cancer pain in patients with thoracic malignancies. PMID:25313295

  7. Magnetocubosomes for the delivery and controlled release of therapeutics.

    PubMed

    Montis, Costanza; Castroflorio, Benedetta; Mendozza, Marco; Salvatore, Annalisa; Berti, Debora; Baglioni, Piero

    2015-07-01

    The design of nanostructured drug delivery systems (DDS) that improve the efficacy of therapeutic principles by enhancing their biocompatibility, bioavailability and targeting, has been the focus of extensive research over the past years. Of particular relevance in this field is the development of multifunctional architectures that can deliver different therapeutics or diagnostic agents and release them in a controlled way. In this study we report on the design, preparation and characterization of a DDS where hydrophobic Fe3O4 magnetic nanoparticles (NPs) are included in the bilayer of bicontinuous cubic lipid nanoparticles of Glyceryl Monooleate (GMO). The "magnetocubosomes" are characterized and investigated in terms of their ability to encapsulate and release both hydrophilic and hydrophobic model drugs. For the first time Fluorescence Correlation Spectroscopy (FCS) is used to study the diffusion of encapsulated molecules inside the bicontinuous cubic phase and to monitor their release from the matrix towards the aqueous phase. In addition, we show with the same technique that magnetocubosomes are responsive to a low frequency alternating magnetic field (LF-AMF), which acts as an external trigger to boost the release of model drugs confined in the cubic phase. Magnetocubosomes, reported for the first time in this paper, represent a novel biocompatible, multifunctional and responsive DDS. PMID:25533536

  8. Stable Ultrathin-Shell Double Emulsions for Controlled Release.

    PubMed

    Zhao, Chun-Xia; Chen, Dong; Hui, Yue; Weitz, David A; Middelberg, Anton P J

    2016-06-01

    Double emulsions are normally considered as metastable systems and this limit in stability restricts their applications. To enhance their stability, the outer shell can be converted into a mechanically strong layer, for example, a polymeric layer, thus allowing improved performance. This conversion can be problematic for food and drug applications, as a toxic solvent is needed to dissolve the polymer in the middle phase and a high temperature is required to remove the solvent. This process can also be highly complex, for example, involving UV initiation of polymeric monomer crosslinking. In this study, we report the formation of biocompatible, water-in-oil-in-water (W/O/W) double emulsions with an ultrathin layer of fish oil. We demonstrate their application for the encapsulation and controlled release of small hydrophilic molecules. Without a trigger, the double emulsions remained stable for months, and the release of small molecules was extremely slow. In contrast, rapid release was achieved by osmolarity shock, leading to complete release within 2 h. This work demonstrates the significant potential of double emulsions, and provides new insights into their stability and practical applications. PMID:26934572

  9. Drug-drug interaction between oxycodone and adjuvant analgesics in blood-brain barrier transport and antinociceptive effect.

    PubMed

    Nakazawa, Yusuke; Okura, Takashi; Shimomura, Keita; Terasaki, Tetsuya; Deguchi, Yoshiharu

    2010-01-01

    To examine possible blood-brain barrier (BBB) transport interactions between oxycodone and adjuvant analgesics, we firstly screened various candidates in vitro using [(3)H]pyrilamine, a substrate of the oxycodone transporter, as a probe drug. The uptake of [(3)H]pyrilamine by conditionally immortalized rat brain capillary endothelial cells (TR-BBB13) was inhibited by antidepressants (amitriptyline, imipramine, clomipramine, amoxapine, and fluvoxamine), antiarrhythmics (mexiletine, lidocaine, and flecainide), and ketamine. On the other hand, antiepileptics (carbamazepine, phenytoin, and clonazepam) and corticosteroids (dexamethasone and prednisolone) did not inhibit [(3)H]pyrilamine uptake, with the exception of sodium valproate. The uptake of oxycodone was significantly inhibited in a concentration-dependent manner by amitriptyline, fluvoxamine and mexiletine with K(i) values of 13, 65, and 44 microM, respectively. These K(i) values are 5-300 times greater than the human therapeutic plasma concentrations. Finally, we evaluated in vivo interaction between oxycodone and amitriptyline in mice. Antinociceptive effects of oxycodone were increased by coadministration of amitriptyline. The oxycodone concentrations in plasma and brain were not changed by coadministration of amitriptyline. Overall, the results suggest that several adjuvant analgesics may interact with the BBB transport of oxycodone at relatively high concentrations. However, it is unlikely that there would be any significant interaction at therapeutically or pharmacologically relevant concentrations. PMID:19499573

  10. Vaccine adjuvants - Current status and prospects on controlled release adjuvancity.

    PubMed

    Sivakumar, S M; Safhi, Mohammed M; Kannadasan, M; Sukumaran, N

    2011-10-01

    The strategy of World Health Organization is to develop efficient and inexpensive vaccine against various infectious diseases amongst children's population. Vaccination is considered as the most cost effective health intervention known to public. Since 90 years various substances have been added in vaccine formulation but still alum is considered as the safest adjuvant for human use licensed by United States Food and Drug Administration. MF 59 and ASO4 are the adjuvants were developed recently and approved for human use. Due to poor adjuvancity, conventional vaccines require multiple recall injection at approximately time intervals to attain optimal immune response. For past approximately two decades the vaccine research has been focused towards the alternation of alum type of adjuvant in order to increase the immunogenicity. The development of new vaccines, is more efficacious or easier to deliver, or both have become an area of research that can certainly benefit from controlled release technology. Especially, the conversion of multiple administration vaccine into single administration vaccine may represent an improved advancement towards the betterment of human health care and welfare. Biodegradable polymer microparticles have been evaluated for delivering antigens in native form, sustained release keeping in mind the safety aspects. In this article we review the overall concept of adjuvants in vaccine technology with special focus towards the prospects of controlled release antigens. PMID:23960760

  11. Controlling the release of peptide antimicrobial agents from surfaces.

    PubMed

    Shukla, Anita; Fleming, Kathleen E; Chuang, Helen F; Chau, Tanguy M; Loose, Christopher R; Stephanopoulos, Gregory N; Hammond, Paula T

    2010-03-01

    Medical conditions are often exacerbated by the onset of infection caused by hospital dwelling bacteria such as Staphylococcus aureus. Antibiotics taken orally or intravenously can require large and frequent doses, further contributing to the sharp rise in resistant bacteria observed over the past several decades. These existing antibiotics are also often ineffective in preventing biofilm formation, a common cause of medical device failure. Local delivery of new therapeutic agents that do not allow bacterial resistance to occur, such as antimicrobial peptides, could alleviate many of the problems associated with current antibacterial treatments. By taking advantage of the versatility of layer-by-layer assembly of polymer thin films, ponericin G1, an antimicrobial peptide known to be highly active against S. aureus, was incorporated into a hydrolytically degradable polyelectrolyte multilayer film. Several film architectures were examined to obtain various drug loadings that ranged from 20 to 150 microg/cm2. Release was observed over approximately ten days, with varying release profiles, including burst as well as linear release. Results indicated that film-released peptide did not suffer any loss in activity against S. aureus and was able to inhibit bacteria attachment, a necessary step in preventing biofilm formation. Additionally, all films were found to be biocompatible with the relevant wound healing cells, NIH 3T3 fibroblasts and human umbilical vein endothelial cells. These films provide the level of control over drug loading and release kinetics required in medically relevant applications including coatings for implant materials and bandages, while eliminating susceptibility to bacterial resistance. PMID:20004967

  12. Novel Thermogelling Dispersions of Polymer Nanoparticles for Controlled Protein Release

    PubMed Central

    Cai, Tong; Hu, Peter D.; Sun, Manwu; Zhou, Jun; Tsai, Yi-Ting; Baker, David; Tang, Liping

    2012-01-01

    A novel poly(oligo(ethylene glycol) methyl ether methacrylate-co-oligo(ethylene glycol) ethyl ether methacrylate)/ poly(acrylic acid) interpenetrating network (IPN) nanoparticle was synthesized. The temperature-responsive properties of the IPN nanoparticles were investigated by dynamic light scattering method. Atomic force microscopic images confirm the homogenous and mono-disperse morphology of the IPN nanoparticles. Both visual observation and viscosity testing demonstrated that the IPN nanoparticles exhibit thermogelling properties at body temperature, 37°C. Subsequent studies verified that such temperature sensitive properties of IPN nanoparticles allow their ease of injection and then slow release of model proteins, both in vitro and in vivo. Histological analysis showed that our IPN implants exerted minimal inflammation following subcutaneous implantation. Our results support that, by simply mixing with proteins of interest, the novel IPN nanoparticles can be used to form in situ thermogelling devices for controlled protein release. PMID:22349097

  13. Thermoresponsive double network micropillared hydrogels for controlled cell release.

    PubMed

    Fei, Ruochong; Hou, Huijie; Munoz-Pinto, Dany; Han, Arum; Hahn, Mariah S; Grunlan, Melissa A

    2014-09-01

    Thermoresponsive poly(N-isopropylacrylamide) hydrogels (PNIPAAm) have been widely used for controlled cell detachment. In this study, cell release is enhanced via deswelling with a two-pronged approach combining a double network (DN) design and micropatterning. PNIPAAm hydrogels are prepared as DNs comprised of a tightly crosslinked 1st network and a loosely crosslinked 2nd network. Moreover, the PNIPAAm DN hydrogels are prepared as both planar 1.5 mm-thick slabs as well as micropillar arrays (≈200 μm pillar diameter). Compared to the corresponding conventional single network (SN) hydrogels, DN hydrogels exhibit enhanced thermosensitivity and cell release efficiency, particularly for the micropillar arrays. PMID:24956117

  14. Chitosan hydrogels for chondroitin sulphate controlled release: an analytical characterization.

    PubMed

    Bianchera, Annalisa; Salomi, Enrico; Pezzanera, Matteo; Ruwet, Elisabeth; Bettini, Ruggero; Elviri, Lisa

    2014-01-01

    This paper provides an analytical characterization of chitosan scaffolds obtained by freeze-gelation toward the uptake and the controlled release of chondroitin sulphate (CS), as cartilage repair agent, under different pH conditions. Scanning electron microscopy (SEM), attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), and liquid chromatography-UV spectrophotometry (LC-UV) techniques were exploited to obtain qualitative and quantitative descriptions of polymer and drug behaviour in the biomaterial. As for morphology, SEM analysis allowed the evaluation of scaffold porosity in terms of pore size and distribution both at the surface (Feret diameter 58 ± 19 μm) and on the cross section (Feret diameter 106 ± 51 μm). LC and ATR-FTIR evidenced a pH-dependent CS loading and release behaviour, strongly highlighting the role of electrostatic forces on chitosan/chondroitin sulphate interactions. PMID:25614850

  15. Optical control of insulin release using a photoswitchable sulfonylurea

    PubMed Central

    Broichhagen, Johannes; Schönberger, Matthias; Cork, Simon C.; Frank, James A.; Marchetti, Piero; Bugliani, Marco; Shapiro, A. M. James; Trapp, Stefan; Rutter, Guy A.; Hodson, David J.; Trauner, Dirk

    2014-01-01

    Sulfonylureas are widely prescribed for the treatment of type 2 diabetes mellitus (T2DM). Through their actions on ATP-sensitive potassium (KATP) channels, sulfonylureas boost insulin release from the pancreatic beta cell mass to restore glucose homeostasis. A limitation of these compounds is the elevated risk of developing hypoglycemia and cardiovascular disease, both potentially fatal complications. Here, we describe the design and development of a photoswitchable sulfonylurea, JB253, which reversibly and repeatedly blocks KATP channel activity following exposure to violet-blue light. Using in situ imaging and hormone assays, we further show that JB253 bestows light sensitivity upon rodent and human pancreatic beta cell function. Thus, JB253 enables the optical control of insulin release and may offer a valuable research tool for the interrogation of KATP channel function in health and T2DM. PMID:25311795

  16. Chitosan Hydrogels for Chondroitin Sulphate Controlled Release: An Analytical Characterization

    PubMed Central

    Bianchera, Annalisa; Salomi, Enrico; Pezzanera, Matteo; Ruwet, Elisabeth; Bettini, Ruggero; Elviri, Lisa

    2014-01-01

    This paper provides an analytical characterization of chitosan scaffolds obtained by freeze-gelation toward the uptake and the controlled release of chondroitin sulphate (CS), as cartilage repair agent, under different pH conditions. Scanning electron microscopy (SEM), attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), and liquid chromatography-UV spectrophotometry (LC-UV) techniques were exploited to obtain qualitative and quantitative descriptions of polymer and drug behaviour in the biomaterial. As for morphology, SEM analysis allowed the evaluation of scaffold porosity in terms of pore size and distribution both at the surface (Feret diameter 58 ± 19 μm) and on the cross section (Feret diameter 106 ± 51 μm). LC and ATR-FTIR evidenced a pH-dependent CS loading and release behaviour, strongly highlighting the role of electrostatic forces on chitosan/chondroitin sulphate interactions. PMID:25614850

  17. Controlled release of ibuprofen by meso–macroporous silica

    SciTech Connect

    Santamaría, E. Maestro, A.; Porras, M.; Gutiérrez, J.M.; González, C.

    2014-02-15

    Structured meso–macroporous silica was successfully synthesized from an O/W emulsion using decane as a dispersed phase. Sodium silicate solution, which acts as a silica source and a poly(ethylene oxide)–poly(propylene oxide)–poly(ethylene oxide) (EO{sub 19}PO{sub 39}EO{sub 19}) denoted as P84 was used in order to stabilize the emulsion and as a mesopore template. The materials obtained were characterized through transmission electron microscopy (TEM), scanning electron microscopy (SEM), small-angle X-ray diffraction scattering (SAXS) and nitrogen adsorption–desorption isotherms. Ibuprofen (IBU) was selected as the model drug and loaded into ordered meso–macroporous materials. The effect of the materials’ properties on IBU drug loading and release was studied. The results showed that the loading of IBU increases as the macropore presence in the material is increased. The IBU adsorption process followed the Langmuir adsorption isotherm. A two-step release process, consisting of an initial fast release and then a slower release was observed. Macropores enhanced the adsorption capacity of the material; this was probably due to the fact that they allowed the drug to access internal pores. When only mesopores were present, ibuprofen was probably adsorbed on the mesopores close to the surface. Moreover, the more macropore present in the material, the slower the release behaviour observed, as the ibuprofen adsorbed in the internal pores had to diffuse along the macropore channels up to the surface of the material. The material obtained from a highly concentrated emulsion was functionalized with amino groups using two methods, the post-grafting mechanism and the co-condensation mechanism. Both routes improve IBU adsorption in the material and show good behaviour as a controlled drug delivery system. - Graphical abstract: Ibuprofen release profiles for the materials obtained from samples P84{sub m}eso (black diamonds), P84{sub 2}0% (white squares), P84{sub 5

  18. Graphene as a photothermal switch for controlled drug release

    NASA Astrophysics Data System (ADS)

    Matteini, Paolo; Tatini, Francesca; Cavigli, Lucia; Ottaviano, Stefania; Ghini, Giacomo; Pini, Roberto

    2014-06-01

    Graphene has recently emerged as a novel material in the biomedical field owing to its optical properties, biocompatibility, large specific surface area and low cost. In this paper, we provide the first demonstration of the possibility of using light to remotely trigger the release of drugs from graphene in a highly controlled manner. Different drugs including chemotherapeutics and proteins are firmly adsorbed onto reduced graphene oxide (rGO) nanosheets dispersed in a biopolymer film and then released by individual millisecond-long light pulses generated by a near infrared (NIR) laser. Here graphene plays the dual role of a versatile substrate for temporary storage of drugs and an effective transducer of NIR-light into heat. Drug release appears to be narrowly confined within the size of the laser spot under noninvasive conditions and can be precisely dosed depending on the number of pulses. The approach proposed paves the way for tailor-made pharmacological treatments of chronic diseases, including cancer, anaemia and diabetes.Graphene has recently emerged as a novel material in the biomedical field owing to its optical properties, biocompatibility, large specific surface area and low cost. In this paper, we provide the first demonstration of the possibility of using light to remotely trigger the release of drugs from graphene in a highly controlled manner. Different drugs including chemotherapeutics and proteins are firmly adsorbed onto reduced graphene oxide (rGO) nanosheets dispersed in a biopolymer film and then released by individual millisecond-long light pulses generated by a near infrared (NIR) laser. Here graphene plays the dual role of a versatile substrate for temporary storage of drugs and an effective transducer of NIR-light into heat. Drug release appears to be narrowly confined within the size of the laser spot under noninvasive conditions and can be precisely dosed depending on the number of pulses. The approach proposed paves the way for tailor

  19. Behavioral Flexibility and Response Selection Are Impaired after Limited Exposure to Oxycodone

    ERIC Educational Resources Information Center

    Seip-Cammack, Katharine M.; Shapiro, Matthew L.

    2014-01-01

    Behavioral flexibility allows individuals to adapt to situations in which rewards and goals change. Potentially addictive drugs may impair flexible decision-making by altering brain mechanisms that compute reward expectancies, thereby facilitating maladaptive drug use. To investigate this hypothesis, we tested the effects of oxycodone exposure on…

  20. Comparison of the pharmacokinetics of oxycodone administered in three Percocet formulations.

    PubMed

    Gammaitoni, Arnold R; Davis, Matthew W

    2002-02-01

    This randomized, open-label, three-period crossover study compared the single-dose pharmacokinetics of three dose levels of oxycodone in combination with acetaminophen (5 mg/325 mg, 7.5 mg/500 mg, or 10 mg/650 mg) in healthy volunteers. Serial 24-hour blood samples were collectedfrom 23 fasting subjects after drug administration. The individual dose levels were evaluated on 3 different days, which were separated by washout periods of at least 7 days, in each subject. Oxycodone AUC(0-t), AUC(0-infinity), and Cmax were dose dependent, whereas tma and t(1/2) were not. The most frequently reported adverse events were dizziness, nausea, headache, pruritus, and vomiting. Most adverse events were mild, and all were self-limiting. Only dizziness occurred in a dose-related manner. Increasing dose levels of oxycodone/acetaminophen provides proportional increases in oxycodone Cmax and AUC. Adverse events were predictable based on the opioid pharmacologic actions of this agent. PMID:11831542

  1. Controlled release matrix tablets of glipizide: Influence of different grades of ethocel and Co-excipient on drug release.

    PubMed

    Mehsud, Saif Ullah; Khan, Gul Majid; Hussain, Abid; Akram, Muhammad; Akhlaq, Muhammad; Khan, Kamran Ahmad; Shakoor, Abdul

    2016-05-01

    The aim of the current study was to formulate and evaluate glipizide controlled release matrix tablets by means of different grades of polymer Ethoceland different co-excipients in order to evaluate their effect on drug release profiles during in vitro dissolution studies. Type II diabetes mellitus is usually treated with Glipizide. Glipizide belongs to sulfonylurea group. Gastric disturbance and severe hypoglycemia has been observed after taking glipizide orally. To overcome these problems, controlled release matrices were developed using different grades of ethyl cellulose polymer with a drug-polymer ratio of 1:3by the direct compression method. The effect on drug release of partial replacement of lactose by different co-excipients, HPMC K100M, starch and CMC, were also studied. Diameter, thickness, hardness, friability, weight variations, drug contents of formulations were tested, these properties were within prescribed limits. Co-excipients and polymer containing formulations were compared to the without co-excipients and polymer containing formulations with respect to their release profile. After a 24-hour release study, ethyl cellulose polymer containing formulation exhibited prolonged release for 5-16 hours; however the polymer Ethocel (R) standard FP 7 Premium without co-excipient containing formulation exhibited controlled release for 24 hours. Incompatibility was investigated between drugs, co-excipient DSC and polymer study was performed and any type of interaction was not found. Different kinetic models were used to study the release mechanism. An enhanced release rate was observed in case of excipients containing formulations. PMID:27166548

  2. Thermal post-treatment alters nutrient release from a controlled-release fertilizer coated with a waterborne polymer.

    PubMed

    Zhou, Zijun; Du, Changwen; Li, Ting; Shen, Yazhen; Zhou, Jianmin

    2015-01-01

    Controlled-release fertilizers (CRF) use a controlled-release technology to enhance the nutrient use efficiency of crops. Many factors affect the release of nutrients from the waterborne polymer-coated CRF, but the effects of thermal post-treatments remain unclear. In this study, a waterborne polyacrylate-coated CRF was post-treated at different temperatures (30 °C, 60 °C, and 80 °C) and durations (2, 4, 8, 12, and 24 h) after being developed in the Wurster fluidized bed. To characterize the polyacrylate membrane, and hence to analyze the mechanism of nutrient release, Fourier transform mid-infrared spectroscopy, scanning electron microscopy, and atomic force microscopy were employed. The nutrient-release model of CRF post-treated at 30 °C was the inverse "L" curve, but an increased duration of the post-treatment had no effect. The nutrient-release model was "S" curve and nutrient-release period was enhanced at higher post-treatment temperatures, and increased post-treatment duration lengthened slowed nutrient release due to a more compact membrane and a smoother membrane surface as well as a promoted crosslinking action. CRF equipped with specified nutrient-release behaviors can be achieved by optimizing the thermal post-treatment parameters, which can contribute to the development and application of waterborne polymer-coated CRF and controlled-release technologies. PMID:26348791

  3. Thermal post-treatment alters nutrient release from a controlled-release fertilizer coated with a waterborne polymer

    NASA Astrophysics Data System (ADS)

    Zhou, Zijun; Du, Changwen; Li, Ting; Shen, Yazhen; Zhou, Jianmin

    2015-09-01

    Controlled-release fertilizers (CRF) use a controlled-release technology to enhance the nutrient use efficiency of crops. Many factors affect the release of nutrients from the waterborne polymer-coated CRF, but the effects of thermal post-treatments remain unclear. In this study, a waterborne polyacrylate-coated CRF was post-treated at different temperatures (30 °C, 60 °C, and 80 °C) and durations (2, 4, 8, 12, and 24 h) after being developed in the Wurster fluidized bed. To characterize the polyacrylate membrane, and hence to analyze the mechanism of nutrient release, Fourier transform mid-infrared spectroscopy, scanning electron microscopy, and atomic force microscopy were employed. The nutrient-release model of CRF post-treated at 30 °C was the inverse “L” curve, but an increased duration of the post-treatment had no effect. The nutrient-release model was “S” curve and nutrient-release period was enhanced at higher post-treatment temperatures, and increased post-treatment duration lengthened slowed nutrient release due to a more compact membrane and a smoother membrane surface as well as a promoted crosslinking action. CRF equipped with specified nutrient-release behaviors can be achieved by optimizing the thermal post-treatment parameters, which can contribute to the development and application of waterborne polymer-coated CRF and controlled-release technologies.

  4. Thermal post-treatment alters nutrient release from a controlled-release fertilizer coated with a waterborne polymer

    PubMed Central

    Zhou, Zijun; Du, Changwen; Li, Ting; Shen, Yazhen; Zhou, Jianmin

    2015-01-01

    Controlled-release fertilizers (CRF) use a controlled-release technology to enhance the nutrient use efficiency of crops. Many factors affect the release of nutrients from the waterborne polymer-coated CRF, but the effects of thermal post-treatments remain unclear. In this study, a waterborne polyacrylate-coated CRF was post-treated at different temperatures (30 °C, 60 °C, and 80 °C) and durations (2, 4, 8, 12, and 24 h) after being developed in the Wurster fluidized bed. To characterize the polyacrylate membrane, and hence to analyze the mechanism of nutrient release, Fourier transform mid-infrared spectroscopy, scanning electron microscopy, and atomic force microscopy were employed. The nutrient-release model of CRF post-treated at 30 °C was the inverse “L” curve, but an increased duration of the post-treatment had no effect. The nutrient-release model was “S” curve and nutrient-release period was enhanced at higher post-treatment temperatures, and increased post-treatment duration lengthened slowed nutrient release due to a more compact membrane and a smoother membrane surface as well as a promoted crosslinking action. CRF equipped with specified nutrient-release behaviors can be achieved by optimizing the thermal post-treatment parameters, which can contribute to the development and application of waterborne polymer-coated CRF and controlled-release technologies. PMID:26348791

  5. Controlled release of photoswitch drugs by degradable polymer microspheres

    PubMed Central

    Groynom, Rebecca; Shoffstall, Erin; Wu, Larry S.; Kramer, Richard H.; Lavik, Erin B.

    2016-01-01

    Background QAQ and DENAQ are synthetic photoswitch compounds that change conformation in response to light, altering current flow through voltage-gated ion channels in neurons. These compounds are drug candidates for restoring light sensitivity in degenerative blinding diseases such as AMD. Purpose However, these photoswitch compounds are cleared from the eye within several days, they must be administered through repeated intravitreal injections. Therefore, we are investigating local, sustained delivery formulations to constantly replenish these molecules and have the potential to restore sight. Methods Here, we encapsulate QAQ and DENAQ into several molecular weights of PLGA through an emulsion technique to assess the viability of delivering the compounds in their therapeutic window over many weeks. We characterize the loading efficiency, release profile, and bioactivity of the compounds after encapsulation. Results A very small burst release was observed for all of the formulations with the majority being delivered over the following two months. The lowest molecular weight PLGA led to the highest loading and most linear delivery for both QAQ and DENAQ. Bioactivity was retained for both compounds across the polymers. Conclusion These results present encapsulation into polymers by emulsion as a viable option for controlled release of QAQ and DENAQ. PMID:26453166

  6. Electrically controlled drug release from nanostructured polypyrrole coated on titanium

    NASA Astrophysics Data System (ADS)

    Sirivisoot, Sirinrath; Pareta, Rajesh; Webster, Thomas J.

    2011-02-01

    Previous studies have demonstrated that multi-walled carbon nanotubes grown out of anodized nanotubular titanium (MWNT-Ti) can be used as a sensing electrode for various biomedical applications; such sensors detected the redox reactions of certain molecules, specifically proteins deposited by osteoblasts during extracellular matrix bone formation. Since it is known that polypyrrole (PPy) can release drugs upon electrical stimulation, in this study antibiotics (penicillin/streptomycin, P/S) or an anti-inflammatory drug (dexamethasone, Dex), termed PPy[P/S] or PPy[Dex], respectively, were electrodeposited in PPy on titanium. The objective of the present study was to determine if such drugs can be released from PPy on demand and (by applying a voltage) control cellular behavior important for orthopedic applications. Results showed that PPy films possessed nanometer-scale roughness as analyzed by atomic force microscopy. X-ray photoelectron spectroscopy confirmed the presence of P/S and Dex encapsulated within the PPy films. Results from cyclic voltammetry showed that 80% of the drugs were released on demand when sweep voltages were applied for five cycles at a scan rate of 0.1 V s - 1. Furthermore, osteoblast (bone-forming cells) and fibroblast (fibrous tissue-forming cells) adhesion were determined on the PPy films. Results showed that PPy[Dex] enhanced osteoblast adhesion after 4 h of culture compared to plain Ti. PPy-Ti (with or without anionic drug doping) inhibited fibroblast adhesion compared to plain Ti. These in vitro results confirmed that electrodeposited PPy[P/S] and PPy[Dex] can release drugs on demand to potentially fight bacterial infection, reduce inflammation, promote bone growth or reduce fibroblast functions, further implicating the use of such materials as implant sensors.

  7. Formulation and evaluation of olanzapine matrix pellets for controlled release

    PubMed Central

    Vishal Gupta, N.; Balamuralidhara, V.; Mohammed Khan, S.

    2011-01-01

    Background and the purpose of the study Olanzapine is an antipsychotic used in treatment of schizophrenia. This research was carried out to design oral controlled release matrix pellets of water insoluble drug Olanzapine (OZ), using blend of Sodium Alginate (SA) and Glyceryl Palmito-Stearate (GPS) as matrix polymers, micro crystalline cellulose (MCC) as spheronizer enhancer and Sodium Lauryl Sulphate (SLS) as pore forming agent. Methods OZ formulations were developed by the pelletization technique by drug loaded pellets and characterized with regard to the drug content, size distribution, Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FTIR) and X-ray Diffraction study (XRD). Stability studies were carried out on the optimized formulation for a period of 90 days at 40±2 °C and 75±5% relative humidity. Results and major conclusion The drug content was in the range of 93.34–98.12%. The mean particle size of the drug loaded pellets was in the range 1024 to 1087µm. SEM photographs and calculated sphericity factor confirmed that the prepared formulations were spherical in nature. The compatibility between drug and polymers in the drug loaded pellets was confirmed by DSC and FTIR studies. Stability studies indicated that pellets are stable. XRD patterns revealed the crystalline nature of the pure OZ. Loose surface crystal study indicated that crystalline OZ is present in all formulations and more clear in formulation F5. Drug release was controlled for more than 24 hrs and mechanism of the drug release followed by Fickian diffusion. It may be concluded that F5 is an ideal formulation for once a day administration. PMID:22615665

  8. Controlled iodine release from polyurethane sponges for water decontamination.

    PubMed

    Aviv, Oren; Laout, Natalia; Ratner, Stanislav; Harik, Oshrat; Kunduru, Konda Reddy; Domb, Abraham J

    2013-12-28

    Iodinated polyurethane (IPU) sponges were prepared by immersing sponges in aqueous/organic solutions of iodine or exposing sponges to iodine vapors. Iodine was readily adsorbed into the polymers up to 100% (w/w). The adsorption of iodine on the surface was characterized by XPS and SEM analyses. The iodine loaded IPU sponges were coated with ethylene vinyl acetate (EVA), in order to release iodine in a controlled rate for water decontamination combined with active carbon cartridge, which adsorbs the iodine residues after the microbial inactivation. The EVA coated IPU were incorporated in a water purifier and tested for iodine release to water and for microbial inactivation efficiency according to WQA certification program against P231/EPA for 250l, using 25l a day with flow rate of 6-8min/1l. The antimicrobial activity was also studied against Escherichia coli and MS2 phage. Bacterial results exceeded the minimal requirement for bacterial removal of 6log reduction throughout the entire lifespan. At any testing point, no bacteria was detected in the outlet achieving more than 7.1 to more than 8log reduction as calculated upon the inlet concentration. Virus surrogate, MS2, reduction results varied from 4.11log reduction under tap water, and 5.11log reduction under basic water (pH9) to 1.32 for acidic water (pH5). Controlled and stable iodine release was observed with the EVA coated IPU sponges and was effective in deactivating the bacteria and virus present in the contaminated water and thus, these iodinated PU systems could be used in water purification to provide safe drinking water. These sponges may find applications as disinfectants in medicine. PMID:24096017

  9. Physical and chemical control of released microorganisms at field sites

    SciTech Connect

    Donegan, K.; Seidler, R.; Matyac, C.

    1991-01-01

    An important consideration in the environmental release of a genetically engineered microorganism (GEM) is the capability for reduction or elimination of GEM populations once their function is completed or if adverse environmental effects are observed. The decontamination treatments of burning and biocide application, alone and in combination with tilling, were evaluated for their ability to reduce populations of bacteria released on the phylloplane. Field plots of bush beans sprayed with the bacterium Erwinia herbicola, received the following treatments: (1) control, (2) control + till, (3) burn, (4) burn + till, (5) Kocide (cupric hydroxide), (6) Kocide + till, (7) Agri-strep (streptomycin sulfate), and (8) Agri-strept + till. Leaves and soil from the plots were sampled -1, 1, 5, 8, 12, 15, 19, and 27 days after application of the decontamination treatments. Burning produced a significant and persistent reduction in the number of bacteria whereas tilling, alone or in combination with the biocide treatments, stimulated a significant and persistent reduction in the number of bacteria, whereas tilling, alone or in combination with the biocide treatments, stimulated a significant increase in bacterial populations that persisted for several weeks.

  10. Electrically credible polymer gel for controlled release of drugs

    NASA Astrophysics Data System (ADS)

    Kwon, Ick Chan; Bae, You Han; Kim, Sung Wan

    1991-11-01

    NEW controlled drug-delivery systems are being explored to overcome the disadvantages of conventional dosage forms1. For example, stimulated drug-delivery has been used to overcome the tolerance problems that occur with a constant delivery rate, to mimic the physiological pattern of hormonal concentration and to supply drugs on demand1,2. Stimuli-sensitive polymers, which are potentially useful for pulsed drug delivery, experience changes in either their structure or their chemical properties in response to changes in environmental conditions2. Environmental stimuli include temperature3,4, pH5,6, light (ultraviolet7 or visible8), electric field9-12 or certain chemicals13. Volume changes of stimuli-sensitive gel networks are particularly responsive to external stimuli, but swelling is slow to occur14,15. As well as being useful in the controlled release of drugs, such systems also provide insight into intermolecular interactions16. Here we report on a novel polymeric system, which rapidly changes from a solid state to solution in response to small electric currents, by disintegration of the solid polymer complex into two water-soluble polymers. We show that the modulated release of insulin, and by extension other macromolecules, can be achieved with this polymeric system.

  11. A concise review on smart polymers for controlled drug release.

    PubMed

    Aghabegi Moghanjoughi, Arezou; Khoshnevis, Dorna; Zarrabi, Ali

    2016-06-01

    Design and synthesis of efficient drug delivery systems are of critical importance in health care management. Innovations in materials chemistry especially in polymer field allows introduction of advanced drug delivery systems since polymers could provide controlled release of drugs in predetermined doses over long periods, cyclic and tunable dosages. To this end, researchers have taken advantages of smart polymers since they can undergo large reversible, chemical, or physical fluctuations as responses to small changes in environmental conditions, for instance, in pH, temperature, light, and phase transition. The present review aims to highlight various kinds of smart polymers, which are used in controlled drug delivery systems as well as mechanisms of action and their applications. PMID:26744179

  12. Controlling Hazardous Releases while Protecting Passengers in Civil Infrastructure Systems

    NASA Astrophysics Data System (ADS)

    Rimer, Sara P.; Katopodes, Nikolaos D.

    2015-11-01

    The threat of accidental or deliberate toxic chemicals released into public spaces is a significant concern to public safety, and the real-time detection and mitigation of such hazardous contaminants has the potential to minimize harm and save lives. Furthermore, the safe evacuation of occupants during such a catastrophe is of utmost importance. This research develops a comprehensive means to address such scenarios, through both the sensing and control of contaminants, and the modeling of and potential communication to occupants as they evacuate. A computational fluid dynamics model is developed of a simplified public space characterized by a long conduit (e.g. airport terminal) with unidirectional ambient flow that is capable of detecting and mitigating the hazardous contaminant (via boundary ports) over several time horizons using model predictive control optimization. Additionally, a physical prototype is built to test the real-time feasibility of this computational flow control model. The prototype is a blower wind-tunnel with an elongated test section with the capability of sensing (via digital camera) an injected `contaminant' (propylene glycol smoke), and then mitigating that contaminant using actuators (compressed air operated vacuum nozzles) which are operated by a set of pressure regulators and a programmable controller. Finally, an agent-based model is developed to simulate ``agents'' (i.e. building occupants) as they evacuate a public space, and is coupled with the computational flow control model such that agents must interact with a dynamic, threatening environment. NSF-CMMI #0856438.

  13. Evaluation of a soil incubation method to characterize nitrogen release patterns of slow- and controlled-release fertilizers.

    PubMed

    Medina, L Carolina; Sartain, Jerry B; Obreza, Thomas A; Hall, William L; Thiex, Nancy J

    2014-01-01

    Several technologies have been proposed to characterize the nutrient release patterns of slow-release fertilizers (SRF) and controlled-release fertilizers (CRF) during the last few decades. These technologies have been developed mainly by manufacturers, and are product-specific, based on the regulation and analysis of each SRF and CRF product. Despite previous efforts to characterize SRF and CRF materials, no standardized, validated method exists to assess their nutrient release patterns. However, the increased production and distribution of these materials in specialty and nonspecialty markets requires an appropriate method to verify product claims and material performance. A soil incubation column leaching procedure was evaluated to determine its suitability as a standard method to estimate nitrogen (N) release patterns of SRFs and CRFs during 180 days. The influence of three soil/sand ratios, three incubation temperatures, and four soils on method behavior was assessed using five SRFs and three CRFs. In general, the highest soil/sand ratio increased the N release rate of all materials, but this effect was more marked for the SRFs. Temperature had the greatest influence on N release rates. For CRFs, the initial N release rates and the percentage N released/day increased as temperature increased. For SRFs, raising the temperature from 25 to 35 degreesC increased initial N release rate and the total cumulative N released, and almost doubled the percentage released/day. The percentage N released/day from all products generally increased as the texture of the soil changed from sandy to loamy (lowa>California>Pennsylvania>Florida). The soil incubation technique was demonstrated to be robust and reliable for characterizing N release patterns from SRFs and CRFs. The method was reproducible, and variations in soil/sand ratio, temperature, and soil had little effect on the results. PMID:25051610

  14. Modeling controlled nutrient release from a population of polymer coated fertilizers: statistically based model for diffusion release.

    PubMed

    Shaviv, Avi; Raban, Smadar; Zaidel, Elina

    2003-05-15

    A statistically based model for describing the release from a population of polymer coated controlled release fertilizer (CRF) granules by the diffusion mechanism was constructed. The model is based on a mathematical-mechanistic description of the release from a single granule of a coated CRF accounting for its complex and nonlinear nature. The large variation within populations of coated CRFs poses the need for a statistically based approach to integrate over the release from the individual granules within a given population for which the distribution and range of granule radii and coating thickness are known. The model was constructed and verified using experimentally determined parameters and release curves of polymer-coated CRFs. A sensitivity analysis indicated the importance of water permeability in controlling the lag period and that of solute permeability in governing the rate of linear release and the total duration of the release. Increasing the mean values of normally distributed granule radii or coating thickness, increases the lag period and the period of linear release. The variation of radii and coating thickness, within realistic ranges, affects the release only when the standard deviation is very large or when water permeability is reduced without affecting solute permeability. The model provides an effective tool for designing and improving agronomic and environmental effectiveness of polymer-coated CRFs. PMID:12785533

  15. Controlled release pulmonary administration of curcumin using swellable biocompatible microparticles.

    PubMed

    El-Sherbiny, Ibrahim M; Smyth, Hugh D C

    2012-02-01

    This study involves a promising approach to achieve sustained pulmonary drug delivery. Dry powder particulate carriers were engineered to allow simultaneous aerosol lung delivery, evasion of macrophage uptake, and sustained drug release through a controlled polymeric architecture. Chitosan grafted with PEG was synthesized and characterized (FTIR, EA, DSC and 2D-XRD). Then, a series of respirable amphiphilic hydrogel microparticles were developed via spray drying of curcumin-loaded PLGA nanoparticles with chitosan-grafted-PEG or chitosan. The nanoparticles and microparticles were fully characterized using an array of physicochemical analytical methods including particle size, surface morphology, dynamic swelling, density, moisture content and biodegradation rates. The PLGA nanoparticles and the hydrogel microspheres encapsulating the curcumin-loaded PLGA nanoparticles showed average size of 221-243 nm and 3.1-3.9 μm, respectively. The developed carriers attained high swelling within a few minutes and showed low moisture content as dry powders (0.9-1.8%), desirable biodegradation rates, high drug loading (up to 97%), and good sustained release. An aerosolization study was conducted using a next generation impactor, and promising aerosolization characteristics were shown. In vitro macrophage uptake studies, cytotoxicity and in vitro TNF-α assays were performed for the investigated particles. These assays revealed promising biointeractions for the respirable/swellable nano-micro particles developed in this study as potential carriers for sustained pulmonary drug delivery. PMID:22136259

  16. Development of Active Control Method for Supercooling Releasing of Water

    NASA Astrophysics Data System (ADS)

    Mito, Daisuke; Kozawa, Yoshiyuki; Tanino, Masayuki; Inada, Takaaki

    We have tested the prototype ice-slurry generator that enables both production of supercooled water (-2°C) and releasing of its supercooling simultaneously and continuously in a closed piping system. In the experiment, we adopted the irradiation of ultrasonic wave as an active control method of triggering for supercooling releasing, and evaluated the reliability for a practical use compared with the seed ice-crystal trigger. As the results, it has been confirmed that the ultrasonic wave trigger acts assuredly at the same level of degree of supercooling as that by using the seed ice-crystal Trigger. Moreover, it can be found that the ultrasonic wave trigger has the advantage of removing the growing ice-crystals on the pipe wall at the same time. Finally, we have specified the bombardment condition of ultrasonic wave enough to make continuously the ice-slurry in a closed system as the output surface power density > 31.4kW/m2 and the superficial bombardment time > 4.1sec. We have also demonstrated the continuous ice-slurry making for more than 6hours by using the refrigerator system with the practical scale of 88kW.

  17. Controlled Release Pulmonary Administration of Curcumin Using Swellable Biocompatible Microparticles

    PubMed Central

    El-Sherbiny, Ibrahim M.; Smyth, Hugh D. C.

    2012-01-01

    This study involves a promising approach to achieve sustained pulmonary drug delivery. Dry powder particulate carriers were engineered to allow simultaneous aerosol lung delivery, evasion of macrophage uptake, and sustained drug release through a controlled polymeric architecture. Chitosan grafted with PEG was synthesized and characterized (FTIR, EA, DSC and 2D-XRD). Then, a series of respirable amphiphilic hydrogel microparticles were developed via spray drying of curcumin-loaded PLGA nanoparticles with chitosan-grafted-PEG or chitosan. The nano and microparticles were fully characterized using an array of physicochemical analytical methods including particle size, surface morphology, dynamic swelling, density, moisture content and biodegradation rates. The PLGA nanoparticles and the hydrogel microspheres encapsulating the curcumin-loaded PLGA nanoparticles showed average size of (221-243 nm) and (3.1-3.9 μm), respectively. The developed carriers attained high swelling within a few minutes, showed low moisture content as dry powders (0.9-1.8%), desirable biodegradation rates, high drug loading (up to 97%), and good sustained release. An aerosolization study was conducted using a next generation impactor and promising aerosolization characteristics were shown. In vitro macrophage uptake studies, cytotoxicity and in-vitro TNF-α assays were performed for the investigated particles. These assays revealed promising bio-interactions for the respirable/swellable nano-micro particles developed in this study as potential carriers for sustained pulmonary drug delivery. PMID:22136259

  18. Controlled drug release from biodegradable thermoresponsive physical hydrogel nanofibers.

    PubMed

    Loh, Xian Jun; Peh, Priscilla; Liao, Susan; Sng, Colin; Li, Jun

    2010-04-19

    Hydrogel nanofiber mats based on thermoresponsive multiblock poly(ester urethane)s comprising poly(ethylene glycol) (PEG), poly(propylene glycol) (PPG), and poly(epsilon-caprolactone) (PCL) segments were fabricated by electrospinning. The hydrogel nanofiber mats were more water absorbent under cold conditions and shrunk when exposed to higher temperatures. The rate of protein release could be controlled by changing the temperature of the nanofiber environment. Cell culture studies on the nanofiber mats were carried out using human dermal fibroblasts, and healthy cell morphology was observed. The adherent viable cells were quantified by MTS after rinsing in excess buffer solution. The results showed that these nanofiber scaffolds supported excellent cell adhesion, comparable with the pure PCL nanofibers. The increased hydrophilicity of these hydrogel nanofiber mats led to a more rapid hydrolytic degradation, compared with the pure PCL nanofiber mats. These hydrogel nanofiber scaffolds could potentially be used as thermoresponsive biodegradable supporting structures for skin tissue engineering applications. PMID:20064568

  19. Externally Controlled Triggered-Release of Drug from PLGA Micro and Nanoparticles

    PubMed Central

    Hua, Xin; Tan, Shengnan; Bandara, H. M. H. N.; Fu, Yujie; Liu, Siguo; Smyth, Hugh D. C.

    2014-01-01

    Biofilm infections are extremely hard to eradicate and controlled, triggered and controlled drug release properties may prolong drug release time. In this study, the ability to externally control drug release from micro and nanoparticles was investigated. We prepared micro/nanoparticles containing ciprofloxacin (CIP) and magnetic nanoparticles encapsulated in poly (lactic-co-glycolic acid) PLGA. Both micro/nanoparticles were observed to have narrow size distributions. We investigated and compared their passive and externally triggered drug release properties based on their different encapsulation structures for the nano and micro systems. In passive release studies, CIP demonstrated a fast rate of release in first 2 days which then slowed and sustained release for approximately 4 weeks. Significantly, magnetic nanoparticles containing systems all showed ability to have triggered drug release when exposed to an external oscillating magnetic field (OMF). An experiment where the OMF was turned on and off also confirmed the ability to control the drug release in a pulsatile manner. The magnetically triggered release resulted in a 2-fold drug release increase compared with normal passive release. To confirm drug integrity following release, the antibacterial activity of released drug was evaluated in Pseudomonas aeruginosa biofilms in vitro. CIP maintained its antimicrobial activity after encapsulation and triggered release. PMID:25479357

  20. Antibacterial activities and release kinetics of a newly developed recoverable controlled agent-release system.

    PubMed

    Ehara, A; Torii, M; Imazato, S; Ebisu, S

    2000-03-01

    We attempted to develop a resin with a recoverable antibacterial activity based on the desorption/adsorption of a cationic bactericide by the ion-exchange mechanism. The aims of this study were to investigate the release kinetics of the agent and the antibacterial activity of this newly designed resin system. An experimental resin was prepared by the addition of methacrylic acid as a cation-exchanger and a cationic antibacterial agent, cetylpyridinium chloride (CPC), to triethyleneglycol dimethacrylate. The amount of CPC desorbed from the experimental resin into buffer solutions at pH 4-8 was measured. The adsorption of CPC to control resin and re-adsorption of CPC to the experimental resin, which had once desorbed the agent, were also determined. The antibacterial activity of experimental resin against Streptococcus mutans was evaluated, and the relationship between bacterial acid production and antibacterial effect was assessed. The experimental resin desorbed CPC at pH < or = 6, and the amount of agent desorbed increased with increasing acidity. The control resin adsorbed CPC when immersed in CPC aqueous solution at a rate determined by the concentration of the agent and immersion time. The experimental resin, once desorbed CPC, could re-adsorb the bactericide by being exposed to a solution of the agent. Less plaque formed on the experimental resin, and the growth and survival of S. mutans was inhibited in the condition in which acid was produced. These results demonstrate that the resin system proposed was able to desorb and re-adsorb the cationic bactericide by an ion-exchange mechanism and could show an inhibitory effect on S. mutans growth and plaque formation. PMID:10765955

  1. 76 FR 73679 - Manufacturer of Controlled Substances; Notice of Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-29

    ... controlled substances: Drug Schedule Codeine-N-oxide (9053) I Dihydromorphine (9145) I Morphine-N-oxide (9307... Oxycodone (9143) II Hydromorphone (9150) II Hydrocodone (9193) II Morphine (9300) II Oripavine (9330)...

  2. Combined administration of oxycodone/naloxone in chronic osteo-articular diseases pain therapy.

    PubMed

    Rosa, Palomba; Federica, Miralto; Annamaria, Vinciguerra; Fabiana, Salvato; Anna, Vaccarella

    2014-04-01

    The aim of this study is the analysis of the beneficial impact of using opioid receptor antagonist associated to opioid analgesic on the quality of life in patients suffering from chronic non-cancer pain. We recruited 60 patients suffering from osteo-articular diseases who were randomized into two groups of treatment. The group A was treated with the association of opioid receptor antagonist and opioid agonist, represented by Oxycodone. The group B was treated with the opioid analgesics Oxycodone, transdermal Fentanil, and Hidromorphone, without the opioid antagonist. The end-points assessed were the duration of titration, the average reached dosage, the duration of the stability of dosage and the opioid-induced constipation (OIC) using the BFI. PMID:24809034

  3. Comparison in vitro felodipine release rate from the original versus generic product with controlled release of the drug.

    PubMed

    Vetchy, David; Vetcha, Martina; Rabiskova, Miloslava; Gryczova, Eva; Bartosikova, Lenka

    2007-01-01

    After patent protection of original brand is over, there are a lot of generic products occurring on the pharmaceutical market. It may be the way to reduce the price, but on the other hand, one should expect the same quality and almost identity with original brand, because the development of generic drugs is based on pharmacological properties of the original brand. The aim of this study was to compare the similarity of two products with controlled release of felodipine--generic product Presid and original brand Plendil--which are commercially available in Czech Republic, based on in vitro dissolution testing. The dissolution test in three dissolution media of increasing pH (1.2, 4.5, and 6.5) for the simulation of physiological pH within the gastrointestinal tract confirmed controlled release of felodipine from the original product Plendil ER 5 mg and Plendil ER 10 mg during the period of 24 hours. The release of felodipine from generic products Presid 5 mg and Presid 10 mg was not controlled for 24 hours as it is indicated in the information leaflet. In the generic products, felodipine release was controlled just for 12 or 18 hours and in this respect did not show similarity with the original brand. Since patients take the drug just once a day in the morning, the controlled release of felodipine, which lasts only 12 to 18 hours, can cause insufficient blood pressure control especially in the most critical morning hours and higher cardiovascular risk. PMID:17485960

  4. Factors controlling phosphorus release from sediments in coastal archipelago areas.

    PubMed

    Puttonen, Irma; Kohonen, Tuula; Mattila, Johanna

    2016-07-15

    In coastal archipelago areas of the northern Baltic Sea, significantly higher phosphate concentrations (6.0±4.5μmol/l, mean±SD) were measured in water samples close to the sediment surface compared with those from 1m above the seafloor (1.6±2.0μmol/l). The results indicated notable phosphate release from sediments under the bottom water oxygen concentrations of up to 250μmol/l, especially in areas that had experienced recent temporal fluctuation between oxic and hypoxic/anoxic conditions. No single factor alone was found to control the elevated PO4-P concentrations in the near-bottom water. In addition to the oxygen in the water, the contents of potentially mobile phosphorus fractions, grain-size, the organic content at the sediment surface, and the water depth were all important factors controlling the internal loading of phosphorus. The complexity of this process needs to be accounted for in assessments of the internal loading of phosphorus and in potential mitigation plans. PMID:27184132

  5. Silylated Precision Particles for Controlled Release of Proteins

    PubMed Central

    Khodabandehlou, Khosrow; Kumbhar, Amar S.; Habibi, Sohrab; Pandya, Ashish A.; Luft, J. Christopher; Khan, Saad A.; DeSimone, Joseph M.

    2015-01-01

    With the recent advances in the development of novel protein based therapeutics, controlled delivery of these biologics is an important area of research. Herein, we report the synthesis of microparticles from bovine serum albumin (BSA) as a model protein using Particle Replication in Non-wetting Templates (PRINT) with specific size and shape. These particles were functionalized at room temperature using multifunctional chlorosilane that cross-link the particles to render them to slowly-dissolving in aqueous media. Mass spectrometric study of the reaction products of diisopropyldichlorosilane with individual components of the particles revealed that they are capable of reacting and forming cross-links. Energy dispersive spectroscopy (EDS) and X-ray photoelectron spectroscopy (XPS) were also used to confirm the functionalization of the particles. Cross sectional analysis using focused ion beam (FIB) and EDS proved that the functionalization occurs throughout the bulk of the particles and is not just limited to the surface. Circular dichroism data confirmed that the fraction of BSA molecules released from the particles retains its secondary structure thereby indicating that the system can be used for delivering protein based formulations while controlling the dissolution kinetics. PMID:25742193

  6. Release of Ammonium and Mercury from NOx Controlled Fly Ash

    SciTech Connect

    Schroeder, K.T.; Cardone, C.R.; Kim, A.G

    2007-07-01

    One of the goals of the Department of Energy is to increase the reuse of coal utilization byproducts (CUB) to 50% by 2010. This will require both developing new markets and maintaining traditional ones such as the use of fly ash in concrete. However, the addition of pollution control devices can introduce side-effects that affect the marketability of the CUB. Such can be the case when NOx control is achieved using selective catalytic or non-catalytic reduction (SCR or SNCR). Depending on site-specific details, the ammonia slip can cause elevated levels of NH3 in the fly ash. Disposal of ammoniated fly ash can present environmental concerns related to the amount of ammonia that might be released, the amount of water that might become contaminated, and the extent to which metals might be mobilized by the presence of the ammonia. Ammonia retained in fly ash appears to be present as either an ammonium salt or as a chemisorbed species. Mercury in the leachates correlated to neither the amount of leachable ammonium nor to the total amount of Hg in the ash. The strongest correlation was between the decreases in the amount of Hg leached with increased LOI.

  7. Degradable thermoresponsive nanogels for protein encapsulation and controlled release.

    PubMed

    Bhuchar, Neha; Sunasee, Rajesh; Ishihara, Kazuhiko; Thundat, Thomas; Narain, Ravin

    2012-01-18

    Reversible addition-fragmentation chain transfer (RAFT) polymerization technique was used for the fabrication of stable core cross-linked micelles (CCL) with thermoresponsive and degradable cores. Well-defined poly(2-methacryloyloxyethyl phosphorylcholine), poly(MPC) macroRAFT agent, was first synthesized with narrow molecular weight distribution via the RAFT process. These CCL micelles (termed as nanogels) with hydrophilic poly(MPC) shell and thermoresponsive core consisting of poly(methoxydiethylene glycol methacrylate) (poly(MeODEGM) and poly(2-aminoethyl methacrylamide hydrochloride) (poly(AEMA) were then obtained in a one-pot process by RAFT polymerization in the presence of an acid degradable cross-linker. These acid degradable nanogels were efficiently synthesized with tunable sizes and low polydispersities. The encapsulation efficiencies of the nanogels with different proteins such as insulin, BSA, and β-galactosidase were studied and found to be dependent of the cross-linker concentration, size of protein, and the cationic character of the nanogels imparted by the presence of AEMA in the core. The thermoresponsive nature of the synthesized nanogels plays a vital role in protein encapsulation: the hydrophilic core and shell of the nanogels at low temperature allow easy diffusion of the proteins inside out and, with an increase in temperature, the core becomes hydrophobic and the nanogels are easily separated out with entrapped protein. The release profile of insulin from nanogels at low pH was studied and results were analyzed using bicinchoninic assay (BCA). Controlled release of protein was observed over 48 h. PMID:22171688

  8. Solid lipid budesonide microparticles for controlled release inhalation therapy.

    PubMed

    Mezzena, Matteo; Scalia, Santo; Young, Paul M; Traini, Daniela

    2009-12-01

    A solid lipid microparticle system containing budesonide was prepared by oil in water emulsification followed by spray drying. The solid lipid system was studied in terms of morphology, particle size distribution, crystallinity, thermal properties, aerosol performance, and dissolution/diffusion release. The microparticle system was also compared to conventional spray-dried crystalline and amorphous budesonide samples. The particle size distributions of the crystalline, amorphous, and solid lipid microparticles, measured by laser diffraction, were similar; however, the microparticle morphology was more irregular than the spray-dried drug samples. The thermal response of the solid lipid microparticles suggested polymorphic transition and melting of the lipid, glycerol behenate (at approximately 48 degrees C and approximately 72 degrees C). No budesonide melting or crystallisation peaks were observed, suggesting that the budesonide was integrated into the matrix. X-ray powder diffraction patterns of the crystalline and amorphous budesonide were consistent with previous studies while the solid lipid microparticles showed two peaks, at approximately 21.3 and 23.5 2theta suggesting the metastable sub-alpha and primarily beta' form. Analysis of the in vitro diffusion/dissolution of the formulations was studied using a flow through model and curves analysed using difference/similarity factors and fitted using the Higuchi model. Regression analysis of this data set indicated differences in the t (0.5), where values of 49.7, 35.3, and 136.9 min were observed for crystalline, amorphous, and the solid lipid microparticles, respectively. The aerosol performance (<5 microm), measured by multistage liquid impinger, was 29.5%, 27.3%, and 21.1 +/- 0.6% for the crystalline, amorphous, and the solid lipid microparticles, respectively. This study has shown that solid lipid microparticles may provide a useful approach to controlled release respiratory therapy. PMID:19908147

  9. Radio controlled release apparatus for animal data acquisition devices

    DOEpatents

    Stamps, James Frederick

    2000-01-01

    A novel apparatus for reliably and selectively releasing a data acquisition package from an animal for recovery. The data package comprises two parts: 1) an animal data acquisition device and 2) a co-located release apparatus. One embodiment, which is useful for land animals, the release apparatus includes two major components: 1) an electronics package, comprising a receiver; a decoder comparator, having at plurality of individually selectable codes; and an actuator circuit and 2) a release device, which can be a mechanical device, which acts to release the data package from the animal. To release a data package from a particular animal, a radio transmitter sends a coded signal which is decoded to determine if the code is valid for that animal data package. Having received a valid code, the release device is activated to release the data package from the animal for subsequent recovery. A second embodiment includes floatation means and is useful for releasing animal data acquisition devices attached to sea animals. This embodiment further provides for releasing a data package underwater by employing an acoustic signal.

  10. Effect of preemptive analgesia with intravenous oxycodone in the patients undergoing laparoscopic resection of ovarian tumor

    PubMed Central

    Wang, Na; Wang, Yuantao; Pang, Lei; Wang, Jinguo

    2015-01-01

    Objective: To evaluate the efficacy of preemptive intravenous oxycodone in the patients undergoing laparoscopic resection of ovarian tumor. Methods: Sixty ASA I or II patients undergoing elective laparoscopic resection of ovarian tumor were randomly allocated to one of two groups: Group O (n=30) received intravenous oxycodone (0.1 mg·kg-1) 10 minutes before surgery over 2 minutes, and Group N (n=30) received an equivalent volume of normal saline. All patients received a standardized general anesthesia. MBP and HR at the time of arrival of the operating room (T1), 5 min before pneumoperitoneum (T2), 5 minutes (T3), 10 minutes (T4), and 15 minutes after pneumoperitoneum (T5), and VAS scores at postoperative 2, 4, 8, 12 and 24 hour were recorded. The tramadol consumption and side effects in 24 h after surgery were recorded. Results: VAS pain scores at 2, 4, 8 and 12 hour after operation were significantly lower in Group O (P<0.05). MBP and HR increased significantly due to pneumoperitoneum at T3, T4 and T5, compared with T1 and T2 within Group N, and were higher at T3, T4 and T5 in Group N than at the same time points in Group O. Tramadol consumption was statistically lower in Group O (P=0.0003). Conclusions: Preemptive intravenous oxycodone was an efficient and safe method to reduce intraoperative haemodynamic effect and postoperative pain. PMID:26101479

  11. Effects of Acute and Repeated Administration of Oxycodone and Naloxone-Precipitated Withdrawal on Intracranial Self-Stimulation in Rats.

    PubMed

    Wiebelhaus, Jason M; Walentiny, D Matthew; Beardsley, Patrick M

    2016-01-01

    Incidence of prescription opioid abuse and overdose, often led by oxycodone, continues to increase, producing twice as many overdose deaths as heroin. Surprisingly, preclinical reports relevant to oxycodone's abuse-related effects are relatively sparse considering its history and patient usage. The goal of this study was to characterize dose- and time-dependent effects of acute and repeated oxycodone administration in a frequency-rate intracranial self-stimulation (ICSS) procedure, an assay often predictive of drug-related reinforcing effects, in male Sprague-Dawley rats. We hypothesized that oxycodone would produce a biphasic profile of rate-increasing and rate-decreasing effects maintained by ICSS similar to μ-opioid receptor agonists. Oxycodone (0.03, 0.3, 1, and 3 mg/kg, s.c.) produced dose- and time-dependent alterations on ICSS, with the predicted biphasic profile of rate-increasing effects at lower stimulation frequencies followed by rate-decreasing effects at higher frequencies. Peak effects were observed between 30 and 60 minutes, which were reversed by naloxone pretreatment (30 minutes). Tolerance to rate-decreasing effects was observed over a 5-day period when rats were treated with 1 mg/kg oxycodone twice a day. Subsequently, the dosing regimen was increased to 3 mg/kg twice a day over 10 days, although further marked tolerance did not develop. When then challenged with 10 mg/kg naloxone, a significant suppression below baseline levels of ICSS-maintained responding occurred indicative of dependence that recovered to baseline within 5 hours. The results of this study provide the first report of acute and chronic effects of oxycodone on responding maintained by ICSS presentation and the use of ICSS-maintained responding to characterize its tolerance and dependence effects. PMID:26491062

  12. Design of Controlled Release PLGA Microspheres for Hydrophobic Fenretinide.

    PubMed

    Zhang, Ying; Wischke, Christian; Mittal, Sachin; Mitra, Amitava; Schwendeman, Steven P

    2016-08-01

    Fenretinide, a chemotherapeutic agent for cancer, is water-insoluble and has a very low oral bioavailability. Hence, the objective was to deliver it as an injectable depot and improve the drug solubility and release behavior from poly(lactide-co-glycolide) (PLGA) microspheres by incorporating nonionic surfactants with fenretinide. Enhancement of drug solubilization was observed with Brij 35 or 98, Tween 20, and Pluronic F127, but not Pluronic F68. Co-incorporation of Brij 98 with fenretinide significantly changed the microsphere morphology and improved the fenretinide release profile. The most optimal microsphere formulation, with 20% Brij 98 as excipient, showed an initial in vitro burst around 20% and a sustained release over 28 days in a solubilizing release medium at 37 °C. The effect of addition of MgCO3, drug loading, and polymer blending on the release of fenretinide from PLGA microspheres was also investigated and observed to enhance the drug release. Two sustained release formulations, one incorporating 20% Brij 98 and the other incorporating 3% MgCO3 in the oil phase, were selected for dosing in Sprague-Dawley rats and compared to a single injection of an equivalent dose of fenretinide drug suspension. These two formulations were chosen due to their high encapsulation efficiency, high cumulative release, and desirable in vitro release profile. The drug suspension resulted in a higher initial release in rats compared to the polymeric formulations, however, sustained release was also observed beyond 2 weeks, which may be attributed to the physiological disposition of the drug in vivo. The two PLGA based test formulations provided the desired low initial burst of fenretinide followed by 4 weeks of in vivo sustained release. PMID:27144450

  13. Development of controlled release spheroids using natural polysaccharide as release modifier.

    PubMed

    Kulkarni, Giriraj T; Gowthamarajan, K; Dhobe, Rohan R; Yohanan, Fenni; Suresh, B

    2005-01-01

    A polysaccharide hydrogel was isolated from the seeds of Tamarindus indica (tamarind) and was used as release modifier for the preparation of diclofenac sodium spheroids, using extrusion-spheronization technique. The process was studied for the effect of variables to arrive at spheroids with satisfactory particle shape, size and size-distribution. The prepared spheroids were characterized for surface morphology, qualitative surface porosity, friability, bulk density, and flow properties. The in vitro release studies exhibited a zero-order release kinetics that was confirmed by Higuchi's and Peppas' models. A credible correlation was obtained among swelling index, viscosity, surface roughness of the polysaccharide, and in vitro dissolution profile of the spheroids. In the comparative bioavailability study, we found that the developed spheroids were able to sustain the drug release over 8 hr and could improve the extent of absorption and bioavailability of the drug. PMID:16036714

  14. Control of arachidonic acid release in chick muscle cultures

    NASA Technical Reports Server (NTRS)

    Templeton, G. H.; Padalino, M.; Wright, W.

    1985-01-01

    Cultures from thigh muscles of 12 day old embryonic chicks are utilized to examine arachidonic release, prostaglandin (PG) biosynthesis, and protein synthesis. The preparation of the cultures is described. It is observed that exogenous arachidonic acid is formed into photsphatidylethanolamine and phosphatidylcholine, is released by a calcium ionosphere or phospholiphase simulator, and is the substrate for the biosynthesis of PG; the epidermal growth factor and PGF do not stimulate protein synthesis over the basal levels. The relationship between arachidonate release and melittin is studied. The data reveal that a change in intracellular calcium stimulates phospholiphase activity, arachidonate release, and PG synthesis in chick muscle culture.

  15. Remotely Triggered Scaffolds for Controlled Release of Pharmaceuticals

    PubMed Central

    Roach, Paul; McGarvey, David J.; Lees, Martin R.; Hoskins, Clare

    2013-01-01

    Fe3O4-Au hybrid nanoparticles (HNPs) have shown increasing potential for biomedical applications such as image guided stimuli responsive drug delivery. Incorporation of the unique properties of HNPs into thermally responsive scaffolds holds great potential for future biomedical applications. Here we successfully fabricated smart scaffolds based on thermo-responsive poly(N-isopropylacrylamide) (pNiPAM). Nanoparticles providing localized trigger of heating when irradiated with a short laser burst were found to give rise to remote control of bulk polymer shrinkage. Gold-coated iron oxide nanoparticles were synthesized using wet chemical precipitation methods followed by electrochemical coating. After subsequent functionalization of particles with allyl methyl sulfide, mercaptodecane, cysteamine and poly(ethylene glycol) thiol to enhance stability, detailed biological safety was determined using live/dead staining and cell membrane integrity studies through lactate dehydrogenase (LDH) quantification. The PEG coated HNPs did not show significant cytotoxic effect or adverse cellular response on exposure to 7F2 cells (p < 0.05) and were carried forward for scaffold incorporation. The pNiPAM-HNP composite scaffolds were investigated for their potential as thermally triggered systems using a Q-switched Nd:YAG laser. These studies show that incorporation of HNPs resulted in scaffold deformation after very short irradiation times (seconds) due to internal structural heating. Our data highlights the potential of these hybrid-scaffold constructs for exploitation in drug delivery, using methylene blue as a model drug being released during remote structural change of the scaffold. PMID:23603890

  16. Integrated Luminal and Cytosolic Aspects of the Calcium Release Control

    PubMed Central

    Baran, Irina

    2003-01-01

    We propose here a unitary approach to the luminal and cytosolic control of calcium release. A minimal number of model elements that realistically describe different data sets are combined and adapted to correctly respond to various physiological constraints. We couple the kinetic properties of the inositol 1,4,5 trisphosphate receptor/calcium channel with the dynamics of Ca2+ and K+ in both the lumen and cytosol, and by using a detailed simulation approach, we propose that local (on a radial distance ∼2 μm) calcium oscillations in permeabilized cells are driven by the slow inactivation of channels organized in discrete clusters composed of between six and 15 channels. Moreover, the character of these oscillations is found to be extremely sensitive to K+, so that the cytosolic and luminal calcium variations are in or out of phase if the store at equilibrium has tens or hundreds μM Ca2+, respectively, depending on the K+ gradient across the reticulum membrane. Different patterns of calcium signals can be reproduced through variation of only a few parameters. PMID:12609854

  17. Method of achieving the controlled release of thermonuclear energy

    DOEpatents

    Brueckner, Keith A.

    1986-01-01

    A method of achieving the controlled release of thermonuclear energy by illuminating a minute, solid density, hollow shell of a mixture of material such as deuterium and tritium with a high intensity, uniformly converging laser wave to effect an extremely rapid build-up of energy in inwardly traveling shock waves to implode the shell creating thermonuclear conditions causing a reaction of deuterons and tritons and a resultant high energy thermonuclear burn. Utilizing the resulting energy as a thermal source and to breed tritium or plutonium. The invention also contemplates a laser source wherein the flux level is increased with time to reduce the initial shock heating of fuel and provide maximum compression after implosion; and, in addition, computations and an equation are provided to enable the selection of a design having a high degree of stability and a dependable fusion performance by establishing a proper relationship between the laser energy input and the size and character of the selected material for the fusion capsule.

  18. Poly (lactic-co-glycolic acid) controlled release systems: experimental and modeling insights

    PubMed Central

    Hines, Daniel J.; Kaplan, David L.

    2013-01-01

    Poly-lactic-co-glycolic acid (PLGA) has been the most successful polymeric biomaterial for use in controlled drug delivery systems. There are several different chemical and physical properties of PLGA that impact the release behavior of drugs from PLGA delivery devices. These properties must be considered and optimized in drug release device formulation. Mathematical modeling is a useful tool for identifying, characterizing, and predicting the mechanisms of controlled release. The advantages and limitations of poly (lactic-co-glycolic acid) for controlled release are reviewed, followed by a review of current approaches in controlled release technology that utilize PLGA. Mathematical modeling applied towards controlled release rates from PLGA-based devices will also be discussed to provide a complete picture of state of the art understanding of the control achievable with this polymeric system, as well as the limitations. PMID:23614648

  19. [Rate of controlled-release urea pervasion through membrane determined by ultraviolet spectrophotometry].

    PubMed

    Zuo, Xiu-jin; Wang, Zhen-xin; Dai, Xiao-min; Zhou, Yi; Ma, Xiao-jun

    2006-06-01

    Application of controlled-release nitrogenous fertilizers can improve the efficiency of fertilizers and reduce the environmental pollution. Controlled-release urea (coated urea) is one of the controlled-release nitrogenous fertilizers developed quickly in the recent years. The rate of controlled-release urea pervasion through membrane is the most important index of the capacity of controlled release. There is a maximum absorption at lambda=426 nm with complex in acidic solution, using p-dimethylaminozenzaldehyde as color reagent, and the absorbance exhibits a linear reponses to the urea concentration over the range of 7.5-210 microg x mL(-1). The method for determining the rate of controlled-release urea pervasion through membrane was realized through determining the content of urea in the liquor, the recovery efficiency of the method is 96.1%-103.9%. PMID:16961255

  20. Topical application of a novel oxycodone gel formulation (tocopheryl phosphate mixture) in a rat model of peripheral inflammatory pain produces localized pain relief without significant systemic exposure.

    PubMed

    Smith, Maree T; Wyse, Bruce D; Edwards, Stephen R; El-Tamimy, Mahmoud; Gaetano, Giacinto; Gavin, Paul

    2015-07-01

    This study was designed to assess the analgesic efficacy and systemic exposure of oxycodone administered topically in a novel tocopheryl phosphate mixture (TPM) gel formulation, to the inflamed hindpaws in a rat model of inflammatory pain. Unilateral hindpaw inflammation was induced in male Sprague-Dawley rats by intraplantar (i.pl.) injection of Freund's complete adjuvant (FCA). Mechanical hyperalgesia and hindpaw inflammation were assessed by measuring paw pressure thresholds and hindpaw volume, respectively, just prior to i.pl. FCA and again 5-6 days later. The analgesic effects of oxycodone administered topically (1 mg in TPM gel) or by i.pl. injection (50 μg), were assessed. Systemic oxycodone exposure was assessed over an 8-h postdosing interval following topical application. Skin permeation of oxycodone from the gel formulation was assessed in vitro using Franz diffusion cells. Oxycodone administered topically or by i.pl. injection produced significant (p < 0.05) analgesia in the inflamed hindpaws. Systemic oxycodone exposure was insignificant after topical dosing. The in vitro cumulative skin permeation of oxycodone was linearly related to the amount applied. Topical TPM/oxycodone gel formulations have the potential to alleviate moderate to severe inflammatory pain conditions with minimal systemic exposure, thereby avoiding central nervous system (CNS)-mediated adverse effects associated with oral administration of opioid analgesics. PMID:25995048

  1. Analysis of the release process of phenylpropanolamine hydrochloride from ethylcellulose matrix granules IV.(1)) Evaluation of the controlled release properties for in vivo and in vitro release systems.

    PubMed

    Fukui, Atsuko; Fujii, Ryuta; Yonezawa, Yorinobu; Sunada, Hisakazu

    2007-11-01

    In the pharmaceutical preparation of a controlled release drug, it is very important and necessary to understand the release properties. The dissolution test is a very important and useful method for understanding and predicting drug-release properties. It was readily confirmed in the previous paper that the release process could be assessed quantitatively by a combination of the square-root time law and cube-root law equations for ethylcellulose (EC) matrix granules of phenylpropanolamine hydrochloride (PPA). In this paper EC layered granules were used in addition to EC matrix. The relationship between release property and the concentration of PPA in plasma after administration using beagle dogs were examined. Then it was confirmed that the correlativity for EC layered granules and EC matrix were similar each other. Therefore, it was considered that the dissolution test is useful for prediction of changes in concentration of PPA in the blood with time. And it was suggested that EC layered granules were suitable as a controlled release system as well as EC matrix. PMID:17978513

  2. Materials for Pharmaceutical Dosage Forms: Molecular Pharmaceutics and Controlled Release Drug Delivery Aspects

    PubMed Central

    Mansour, Heidi M.; Sohn, MinJi; Al-Ghananeem, Abeer; DeLuca, Patrick P.

    2010-01-01

    Controlled release delivery is available for many routes of administration and offers many advantages (as microparticles and nanoparticles) over immediate release delivery. These advantages include reduced dosing frequency, better therapeutic control, fewer side effects, and, consequently, these dosage forms are well accepted by patients. Advances in polymer material science, particle engineering design, manufacture, and nanotechnology have led the way to the introduction of several marketed controlled release products and several more are in pre-clinical and clinical development. PMID:20957095

  3. Controlled-release NPK fertilizer encapsulated by polymeric membranes.

    PubMed

    Jarosiewicz, Anna; Tomaszewska, Maria

    2003-01-15

    The commercial granular fertilizer NPK6-20-30 was coated using polysulfone (PSF), polyacrylonitrile (PAN), and cellulose acetate (CA). The coatings were formed from the polymer solutions by the phase inversion technique. Measurements of the thickness and porosity of the prepared coatings and a microphotographic observation of the coatings were performed. The physical properties of the coatings influence the release rate of macronutrients which are present in the core of the coated fertilizer. In the case of PAN coating with 60.45% porosity, prepared from a 16% polymer solution, 100% of NH(4)(+) and P(2)O(5) was released after 4 h of test and 99.7% of K(+) after 5 h of test, whereas in the case of coating with 48.8% porosity, 31.8% of NH(4)(+), 16.7% of P(2)O(5), and 11.6% of K(+) was released after 5 h. In all experiments, different selectivities of the coatings in terms of the release of components were observed. The release of potassium through the coatings made of PSF and PAN was the slowest. The same tendency was observed for the release of nitrogen through a coating of CA. The release of fertilizer active components was the slowest in the case of PSF. The lowest porosity coating was prepared from the 18% PSF solution. PMID:12517104

  4. Controlled release system for ametryn using polymer microspheres: preparation, characterization and release kinetics in water.

    PubMed

    Grillo, Renato; Pereira, Anderson do Espirito Santo; de Melo, Nathalie Ferreira Silva; Porto, Raquel Martins; Feitosa, Leandro Oliveira; Tonello, Paulo Sergio; Dias Filho, Newton L; Rosa, André Henrique; Lima, Renata; Fraceto, Leonardo Fernandes

    2011-02-28

    The purpose of this work was to develop a modified release system for the herbicide ametryn by encapsulating the active substance in biodegradable polymer microparticles produced using the polymers poly(hydroxybutyrate) (PHB) or poly(hydroxybutyrate-valerate) (PHBV), in order to both improve the herbicidal action and reduce environmental toxicity. PHB or PHBV microparticles containing ametryn were prepared and the efficiencies of herbicide association and loading were evaluated, presenting similar values of approximately 40%. The microparticles were characterized by scanning electron microscopy (SEM), which showed that the average sizes of the PHB and PHBV microparticles were 5.92±0.74 μm and 5.63±0.68 μm, respectively. The ametryn release profile was modified when it was encapsulated in the microparticles, with slower and more sustained release compared to the release profile of pure ametryn. When ametryn was associated with the PHB and PHBV microparticles, the amount of herbicide released in the same period of time was significantly reduced, declining to 75% and 87%, respectively. For both types of microparticle (PHB and PHBV) the release of ametryn was by diffusion processes due to anomalous transport (governed by diffusion and relaxation of the polymer chains), which did not follow Fick's laws of diffusion. The results presented in this paper are promising, in view of the successful encapsulation of ametryn in PHB or PHBV polymer microparticles, and indications that this system may help reduce the impacts caused by the herbicide, making it an environmentally safer alternative. PMID:21215514

  5. Use of natural and biobased materials for controlled-release of urea in water: Environmental applications

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Urea pearls were encapsulated in cloisite-based matrices using different natural materials (lignin, beeswax and latex) to control the release of urea over time. It was found that all cloisite-based fertilizer tablets showed better release profiles than neat urea tablets. The best release profile was...

  6. Quantifying Winter Discharge of Controlled Release Fertilizers to Determine Environmental Impact and Plant Uptake

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It is widely believed in the nursery industry that controlled release fertilizers (CRF) release nutrients only when temperatures are greater than ˜4ºC (40ºF). Research recently conducted in Southern California reported CRF continue to release nitrate and phosphorus throughout the winter months. We...

  7. In vivo response to biodegradable controlled antibiotic release systems.

    PubMed

    Korkusuz, F; Korkusuz, P; Ekşioĝlu, F; Gürsel, I; Hasirci, V

    2001-05-01

    In this study, the major goal was to evaluate in vitro and in vivo findings by macroscopy, radiology, and histology to determine the effectiveness of therapy of experimental implant-related osteomyelitis with antibiotic carrier rods constructed of microbial polyesters. The polymers used were poly(3-hydroxybutyrate-co-4-hydroxyvalerate) [P(3-HB-co-4-HB)] and poly(3-hydroxybutyrate-co-3-hydroxy- valerate) [P(3-HB-co-3-HV)]. Both the Sulperazone and the Duocid-P(3-HB-co-4-HB) rods with a drug to polymer ratio of 1:1 (w/w) were effective in treating the bone infection that was experimentally initiated by inoculation of a hemolytic strain of Staphylococcus aureus (coagulase positive; phage type 52/52b) together with metal implants into the medullary area of rabbit tibia. Macroscopical data revealed that the effectiveness of therapy was apparent at week 6 for all categories tested. Radiological findings with Duocid- and Sulperazone-loaded P(3-HB-co-4-HB) rods improved significantly when judged by changes in periosteal elevation, widening of bone shaft, new bone formation, and soft-tissue deformation after 6 weeks of implantation. Histologically the signs of infection were found to subside by weeks 3 and 6. Inflammatory cells were replaced with bone-forming cells upon treatment with Sulperazone-P(3-HB-co-4-HB) and Duocid-P(3-HB-co-4-HB). Osteoblastic activity was prominent. Intramedullary inflammation, although still present, started to be replaced by fibrous or bony tissue. Histological findings presented the subsidence of infection. In summary, the antibiotic-loaded biopolymeric rods appeared to have potential as a new controlled-release system for the treatment of implant related osteomyelitis and chronic osteomyelitis. PMID:11255173

  8. PHYSICAL AND CHEMICAL CONTROL OF RELEASED MICROORGANISMS AT FIELD SITES

    EPA Science Inventory

    An important consideration in the environmental release of a genetically engineered microorganism (GEM) is the capability for reduction or elimination of GEM populations once their function is completed or if adverse environmental effects are observed. In this study the decontami...

  9. Presynaptic control of dopamine release by BETA-phenylethylamine

    SciTech Connect

    Zharikova, A.D.; Godukhin, O.V.

    1985-04-01

    The authors study the effect of extracellular ions (Ca/sup 2 +/, Na/sup 2 +/) on the beta-phenylethylamine (beta-PEA) releasing effect, dependence of this effect on the membrane potential of dopaminergic endings, and the participation of dopamine presynaptic autoreceptors in the realization of the effects of beta-PEA on dopamine (DA) release. Experi ments were carried out on noninbred male albino rats. By means of a microsyringe, (/sup 3/H)-DA hydrochloride was injected. The significance of the difference in levels of (/sup 3/H)-DA release during analogous periods of perfusion in the groups of animals compared was estimated by Student's test. These experiments in vivo thus demonstrated the ability of beta-PEA to regulate DA release in different directions depending on the functional state of the dopaminergic neuron.

  10. Controlled release of donepezil intercalated in smectite clays.

    PubMed

    Park, Jin Kuen; Choy, Young Bin; Oh, Jae-Min; Kim, Ju Young; Hwang, Seong-Ju; Choy, Jin-Ho

    2008-07-01

    The inorganic-organic hybrid for a drug delivery system was successfully realized by intercalating donepezil molecules into smectite clays (laponite XLG, saponite, and montmorillonite). According to the powder XRD patterns, TG profiles, and FT-IR spectra, it was confirmed that donepezil molecules were well stabilized in the interlayer space of clay via mono or double layer stacking. The adsorption amount and molecular structure of donepezil appeared to depend on the cation exchange capacity of the clay, which in turn, tailored the drug release patterns. Especially in the presence of a bulky cationic polymer (Eudragit E-100) in the release media, the release rate was found to be improved due to its effective replacement with intercalated donepezil molecules. Therefore, to formulate a complete drug delivery system, the hybrids were coated with Eudragit E-100 using a spray dryer, which also showed great enhancement in the release rate during a short period of time (180min). PMID:18502063