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Sample records for fentanyl transdermal patches

  1. Fentanyl Transdermal Patch

    MedlinePlus

    ... pain, pain after an operation or medical or dental procedure, or pain that can be controlled by medication that is ... transdermal patch.if you are having surgery, including dental surgery, tell the ... to prevent or treat constipation while you are using fentanyl patches.

  2. Transdermal fentanyl patches in small animals.

    PubMed

    Hofmeister, Erik H; Egger, Christine M

    2004-01-01

    Fentanyl citrate is a potent opioid that can be delivered by the transdermal route in cats and dogs. Publications regarding transdermal fentanyl patches were obtained and systematically reviewed. Seven studies in cats and seven studies in dogs met the criteria for inclusion in this review. Dogs achieved effective plasma concentrations approximately 24 hours after patch application. Cats achieved effective plasma concentrations 7 hours after patch application. In dogs, transdermal fentanyl produced analgesia for up to 72 hours, except for the immediate 0- to 6-hour postoperative period. In cats, transdermal fentanyl produced analgesia equivalent to intermittent butorphanol administration for up to 72 hours following patch application. PMID:15533967

  3. Development and evaluation of a tampering resistant transdermal fentanyl patch.

    PubMed

    Cai, Bing; Engqvist, Håkan; Bredenberg, Susanne

    2015-07-01

    With the increasing number of misuse and abuse of opioids, the resistance to tampering becomes an important attribute for transdermal opioid patches. In this study, drug-containing geopolymer granules were integrated into an adhesive matrix to improve the resistance of fast drug release against some common abuse techniques. Bench testing showed that fentanyl loaded geopolymer granules had better resistance to tampering compared to a commercial fentanyl patch. Moreover, in a pilot in vivo study on a few rats, the granules showed potential to give similar drug plasma concentrations as the commercial fentanyl patch. After integrating geopolymer granules into an adhesive matrix, the new patch showed a better resistance against the investigated tampering tests compared with the commercially available patch. In this study, we showed that incorporating drug loaded geopolymer granules into a patch adhesive has potential to improve the resistance of the fentanyl patch against tampering without compromising the drug release. PMID:25913120

  4. Fatal intravenous fentanyl abuse: four cases involving extraction of fentanyl from transdermal patches.

    PubMed

    Tharp, Amy M; Winecker, Ruth E; Winston, David C

    2004-06-01

    The transdermal fentanyl system delivers a specific dose at a constant rate. Even after the prescribed application time has elapsed, enough fentanyl remains within a patch to provide a potentially lethal dose. Death due to the intravenous injection of fentanyl extracted from transdermal patches has not been previously reported. We present 4 cases in which the source of fentanyl was transdermal patches and was injected. In all of these cases, the victim was a white male who died at home. Case 1 was a 35-year-old with no known history of drug use, who was found by his wife on the floor of his workshop. Police recovered a fentanyl patch, needle, and syringe at the scene. Case 2 was a 38-year-old with a known history of drug use whose family claimed that he was in a treatment program that used fentanyl patches for unknown reasons. His brother found him dead in bed, and law enforcement officers found a hypodermic needle beside the body; a ligature around his left hand, and apparent needle marks between his first and second digits were also noted. Case 3 was a 42-year-old with a recent attempted suicide via overdose who was found dead at his home. An empty box of fentanyl patches, Valium, Ritalin, and 2 syringes were found at the scene. Case 4 was a 39-year-old found by his mother, who admitted to removing a needle with attached syringe from the decedent's arm. Medications at the scene included hydrocodone, alprazolam, zolpidem, and fentanyl patches. All reported deaths were attributed to fentanyl intoxication, with blood concentrations ranging from 5 to 27 microg/L. PMID:15166776

  5. Efficacy of fentanyl transdermal patch in pain control after lower third molar surgery: A preliminary study

    PubMed Central

    Vasovic, Miroslav; Andric, Miroslav; Todorovic, Ljubomir; Kokovic, Vladimir

    2016-01-01

    Background Surgical removal of impacted lower third molars is a common oral surgical procedure, generally followed by moderate to severe postoperative pain. Transdermal drug delivery as a concept offers interesting possibilities for postoperative pain control. The aim of this study was to evaluate the efficacy of transdermal system with fentanyl in relieving pain following impacted lower third molar surgery. Material and Methods Seventeen patients with bilateral impacted lower third molars were included in this preliminary study. For postoperative pain control, patients randomly received a fentanyl patch plus placebo tablet after the first operation and regular (placebo) patch and an analgesic, after the second operation. Analgesia was evaluated during first 24 hours postoperatively according to patients’ reports about time of first pain appearance and additional analgesic consumption. Pain severity was rated using a 10 cm long visual analogue scale (VAS). Results Intensity of postoperative pain and postoperative analgesic consumption were significantly lower after the Fentanyl Transdermal System (FTS) was applied (p<0.05). Duration of postoperative analgesia was significantly higher with FTS when compared to control treatment (p<0.05). Conclusions Based on the results of this preliminary study, transdermal system with fentanyl significantly reduced postoperative pain after third molar surgery. Key words:Analgesia, fentanyl, transdermal administration, third molar surgery, acute pain, postoperative care. PMID:27475691

  6. Can fentanyl transdermal patches prevent the cutaneous hyperpigmentation related to radiotherapy in patients with cancer?

    PubMed

    Mutlu, Hasan

    2016-04-01

    Dermatologic adverse effects related to radiotherapy are one of the most important cosmetic problems and affect the quality of life in patients with cancer. In a male patient with non-small cell lung cancer who received palliative radiotherapy, the hyperpigmentation related to radiotherapy was examined two months later except for fentanyl transdermal patch area. The inhibitory effect of fentanyl on cell cycle may prevent hyperpigmentation related to radiotherapy. PMID:25233883

  7. Exposure to Fentanyl After Transdermal Patch Administration for Cancer Pain Management.

    PubMed

    Bista, Sudeep R; Haywood, Alison; Hardy, Janet; Norris, Ross; Hennig, Stefanie

    2016-06-01

    This study aimed to describe exposure after fentanyl transdermal patch administration in patients with advanced cancer to quantify variability around the exposure. Patients (n  =  56) with advanced cancer who received transdermal fentanyl (Durogesic®; median dose, 50 μg/h; range, 12-200 μg/h) provided venous blood samples (n  =  163) at various times (0.5-72 hours) during several patch application intervals. Plasma fentanyl concentration was determined (median, 0.9 μg/L; range, 0.04-9.7 μg/L) by high-performance liquid chromatography coupled to tandem mass spectrometry. Pharmacokinetic analysis was performed using nonlinear mixed-effects modeling with NONMEM. A 1-compartment distribution model with first-order absorption and elimination described fentanyl exposure after transdermal patch administration. Fentanyl apparent clearance (between-subject variability [BSV], %) was estimated at 122 L/h/70 kg and 38.5%, respectively. The absorption rate constant was 0.013 h(-1) . Between-occasion variability on apparent clearance was 22.0%, which was lower than BSV, suggesting predictable exposure within the same patient and justifying therapeutic drug monitoring. Except for weight-based dosing, no other patient characteristic could be identified to guide initial fentanyl dose selection in patients with advanced cancer. PMID:26381285

  8. Death by band-aid: fatal misuse of transdermal fentanyl patch.

    PubMed

    Bakovic, Marija; Nestic, Marina; Mayer, Davor

    2015-11-01

    We present a case of fatal intoxication by the application of a transdermal fentanyl patch upon a superficial bleeding abrasion of a 2-year-old girl. The grandmother discovered the body of the child in bed at approximately 7 a.m. External examination revealed a properly developed, nourished, and hydrated child, with some vomit in the nostrils and inside the mouth. There was no evidence of trauma besides small contusions and abrasions on the knees, with a patch placed over the largest abrasion. Closer inspection revealed that this was transdermal fentanyl patch. Internal examination and microscopic analysis revealed regurgitation of stomach content, cerebral and pulmonary edema, and liver congestion. Toxicology analysis revealed trace levels of fentanyl in the blood just above the limit of detection (2 ng/mL), while concentrations in the urine, liver, and kidney were approximately 102, 28, and 10 ng/mL, respectively. Investigation discovered that the child injured her knee while playing the evening before. The grandmother applied the patch to cover the injury, unaware that she had used a fentanyl transdermal patch instead of simple band-aid. Although fatal intoxications are uncommon among young children in high-income countries, it is of major interest to raise awareness of such events especially since a great majority of these are preventable. The presented case points at the need for more thorough education of users and more strict rules in prescribing and handling of this potent medicine. As well, we find this case to be a useful contribution to the evaluation of postmortem fentanyl concentrations in fatal intoxication in a small child. PMID:26055040

  9. The transdermal delivery of fentanyl.

    PubMed

    Lane, Majella E

    2013-08-01

    The fentanyl patch is one of the great commercial successes in transdermal drug delivery. The suitability of this molecule for delivery through skin had been identified in the 1970s, and subsequently, a number of transdermal formulations became available on the market. This article reviews the development of fentanyl patch technology with particular emphasis on the pharmacokinetics and disposition of the drug when delivered through the skin. The various patch designs are considered as well as the bioequivalence of the different designs. The influence of heat on fentanyl permeation is highlighted. Post-mortem redistribution of fentanyl is discussed in light of the reported discrepancies in serum levels reported in patients after death compared with therapeutic levels in living subjects. Finally, alternatives to patch technology are considered, and recent novel transdermal formulations are highlighted. PMID:23419814

  10. Fatal intoxication caused by the application of the multiple transdermals patchs of fentanyl

    PubMed Central

    Serghini, Issam; Qamouss, Youssef; Zoubir, Mohamed; Lalaoui, Jaafar Salim; Boughalem, Mohamed

    2015-01-01

    Fentanyl (N-phenyl-N-(1-2-phenylethyl-4-piperidyl)propanamide) is a potent synthetic narcotic analgesic. He has an analgesic effect 100 times greater than that of morphine. The use of transdermal fentanyl delivrery systems has increased over recent years especially in patients with chronic pain who are already treated with high doses of morphine or it is derivate. However, many cases of fentanyl intoxication through a variety of transderrmal systems have been reported. This paper reports a fatality due to excessive administered Fentanyl Sandoz® Matrix 50µg/h transdermal therapeutic systems. PMID:26015841

  11. Noninterventional Study of Transdermal Fentanyl (Fentavera) Matrix Patches in Chronic Pain Patients: Analgesic and Quality of Life Effects

    PubMed Central

    Heim, Manuel

    2015-01-01

    Fentanyl is considered to be an effective, transdermal treatment of chronic, cancer, and noncancer pain. This noninterventional, clinical practice-based study, on 426 patients attending 42 practices, assessed a proprietary, Aloe vera-containing, transdermal fentanyl matrix patch (Fentavera), for its analgesic effects, patients' quality of life (QoL) effects, tolerability, and adhesiveness. Study outcomes were mean changes from baseline of patient (11-point scales) and physician (5-point scales) ratings. After 1 and 2 months treatment, there were significant (P < 0.0001) decreases in patients' ratings of pain intensity, and impairment of walking, general activity, sleep quality, and QoL. For each parameter, the patient response rate was >30% at 2 months (response = 2-point decrease on 11-point rating scale). In a large majority of patients, the physicians rated the matrix patch as good or very good for analgesic effect, systemic and local tolerance, and adhesiveness. There were 30 adverse events in 4.2% of patients and analgesic comedications were reduced during treatment compared to before treatment. It is concluded, from this population-based data, that the proprietary, transdermal fentanyl matrix patch is effective and safe for chronic pain management in clinical practice, with significant positive analgesic and QoL effects, while being well tolerated and exhibiting good or very good adhesiveness. PMID:25861472

  12. Noninterventional study of transdermal fentanyl (fentavera) matrix patches in chronic pain patients: analgesic and quality of life effects.

    PubMed

    Heim, Manuel

    2015-01-01

    Fentanyl is considered to be an effective, transdermal treatment of chronic, cancer, and noncancer pain. This noninterventional, clinical practice-based study, on 426 patients attending 42 practices, assessed a proprietary, Aloe vera-containing, transdermal fentanyl matrix patch (Fentavera), for its analgesic effects, patients' quality of life (QoL) effects, tolerability, and adhesiveness. Study outcomes were mean changes from baseline of patient (11-point scales) and physician (5-point scales) ratings. After 1 and 2 months treatment, there were significant (P < 0.0001) decreases in patients' ratings of pain intensity, and impairment of walking, general activity, sleep quality, and QoL. For each parameter, the patient response rate was >30% at 2 months (response = 2-point decrease on 11-point rating scale). In a large majority of patients, the physicians rated the matrix patch as good or very good for analgesic effect, systemic and local tolerance, and adhesiveness. There were 30 adverse events in 4.2% of patients and analgesic comedications were reduced during treatment compared to before treatment. It is concluded, from this population-based data, that the proprietary, transdermal fentanyl matrix patch is effective and safe for chronic pain management in clinical practice, with significant positive analgesic and QoL effects, while being well tolerated and exhibiting good or very good adhesiveness. PMID:25861472

  13. 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

  14. Clinical pharmacokinetics of transdermal opioids: focus on transdermal fentanyl.

    PubMed

    Grond, S; Radbruch, L; Lehmann, K A

    2000-01-01

    Transdermal delivery allows continuous systemic application of opioids through the intact skin. This review analyses the pharmacokinetic properties of transdermal opioid administration in the context of clinical experience, with a focus on fentanyl. A transdermal therapeutic system (TTS) for fentanyl has been developed. The amount of fentanyl released is proportional to the surface area of the TTS, which is available in different sizes. After the first application of a TTS, a fentanyl depot concentrates in the upper skin layers and it takes several hours until clinical effects are observed. The time from application to minimal effective and maximum serum concentrations is 1.2 to 40 hours and 12 to 48 hours, respectively. Steady state is reached on the third day, and can be maintained as long as patches are renewed. Within each 72-hour period, serum concentrations decrease gradually over the second and third days. When a TTS is removed, fentanyl continues to be absorbed into the systemic circulation from the cutaneous depot. The terminal half-life for TTS fentanyl is approximately 13 to 25 hours. The interindividual variability of serum concentrations, partly caused by different clearance rates, is markedly larger than the intraindividual variability. The effectiveness of TTS fentanyl was first demonstrated in acute postoperative pain. However, the slow pharmacokinetics and large variability of TTS fentanyl, together with the relatively short duration of postoperative pain, precluded adequate dose finding and led to inadequate pain relief or, especially, a high incidence of respiratory depression; such use is now contraindicated. Conversely, in cancer pain, TTS fentanyl offers an interesting alternative to oral morphine, and its effectiveness and tolerability in this indication has been demonstrated by a number of trials. Its usefulness in chronic pain of nonmalignant origin remains to be confirmed in controlled trials. In general, TTS fentanyl produces the same

  15. Rotigotine Transdermal Patch

    MedlinePlus

    ... that causes difficulties with movement, muscle control, and balance) including shaking of parts of the body, stiffness, slowed movements, and problems with balance. Rotigotine transdermal patches are also used to treat ...

  16. Fentanyl Transdermal Patch

    MedlinePlus

    ... sex hormone levels:Health care professionals should conduct laboratory evaluation in patients presenting with such signs or symptoms.For more information visit the FDA website at: http://www.fda.gov/Safety/MedWatch/SafetyInformation and http://www.fda.gov/Drugs/ ...

  17. The Effect of Transdermal Delivery of Fentanyl on Activity in Growing Pigs

    PubMed Central

    Malavasi, LM; Augustsson, H; Jensen-Waern, M; Nyman, G

    2005-01-01

    Recently, decreased activity levels have been observed in pigs treated postoperatively with transdermal delivery of fentanyl (TD-fentanyl) after isoflurane anaesthesia. Whether the change in behaviour is related to opioid-induced sedation or to insufficient pain relief remains to be investigated. This study was therefore undertaken to evaluate the effect of TD-fentanyl 50 μg h-1 on the activity level with and without isoflurane anaesthesia. Eight pigs (25.4 ± 5.2 kg) were submitted to a cross-over study and given two treatments; 1) fentanyl patch applied after 30 minutes of anaesthesia (treatment A/F) and 2) fentanyl patch without anaesthesia (treatment F). The pigs' behaviour was observed from a video recording instantaneously every 10 minutes for 24 h before treatments and up to 72 h after the patch attachment. Venous blood samples were taken 1, 6, 12, 24, 48 and 72 h after the patch application. The behaviour recordings showed that TD-fentanyl did not produce sedation in any pig. No differences were found between the two treatments in activity level, weight gain or serum fentanyl concentration. This concentration measured after 24 h was 0.27 ± 0.11 ng ml-1 and 0.47 ± 0.40 ng ml-1 in the A/F and F group, respectively. In conclusion, transdermal delivery of 50 μg h-1 fentanyl did not cause inactivity in growing pigs. However, the large variations in serum fentanyl concentration indicate that drug absorption from transdermal patches is unpredictable and sometimes deficient. PMID:16261927

  18. Fatal fentanyl patch misuse in a hospitalized patient with a postmortem increase in fentanyl blood concentration.

    PubMed

    Moore, Philip W; Palmer, Robert B; Donovan, Joseph Ward

    2015-01-01

    Opioid-related mortality happens, even in healthcare settings. We describe serial postmortem fentanyl blood concentrations in a hospital inpatient who fatally abused transdermal fentanyl. This is a single-patient case report. A 42-year-old man with lymphoma was started on transdermal fentanyl therapy while hospitalized for chronic abdominal pain. The patient was last seen awake 1.3 h prior to being found apneic and cyanotic. During the resuscitation attempt, a small square-shaped film was removed from the patient's oropharynx. Femoral blood was collected 0.5 and 2 h postmortem, and the measured fentanyl concentration increased from 1.6 to 14 ng/mL. Study limitations include potential laboratory or collection errors and missing data. (i) Providers must be vigilant for signs of fentanyl patch abuse. (ii) Postmortem blood concentrations are not static postmortem, likely secondary to decreasing pH, increased aqueous solubility, and tissue redistribution, and are therefore unlikely to accurately represent antemortem blood concentrations. PMID:25041753

  19. Diclofenac Transdermal Patch

    MedlinePlus

    ... transdermal diclofenac may cause swelling, ulcers, bleeding, or holes in the stomach or intestines. These problems may ... like coffee grounds, blood in the stool, or black and tarry stools.Keep all appointments with your ...

  20. Selegiline Transdermal Patch

    MedlinePlus

    ... heat such as heating pads, electric blankets, heat lamps, saunas, hot tubs, and heated water beds. Do ... last took one of these medications. If you stop using transdermal selegiline, your doctor will probably tell ...

  1. Selegiline Transdermal Patch

    MedlinePlus

    Transdermal selegiline is used to treat depression. Selegiline is in a class of medications called monoamine oxidase (MAO) inhibitors. It works by increasing the amounts of certain natural substances that are needed to maintain ...

  2. Granisetron Transdermal Patch

    MedlinePlus

    ... patch. Each patch is stuck onto a thin plastic liner and a separate rigid plastic film. Do not open the pouch in advance, ... cut the patch into pieces. Peel the thin plastic liner off of the printed side of the ...

  3. Methylphenidate Transdermal Patch

    MedlinePlus

    ... still remove the patch at your regular patch removal time. Do not apply extra patches to make ... room temperature and away from excess heat and moisture (not in the bathroom). Do not refrigerate or ...

  4. Rivastigmine Transdermal Patch

    MedlinePlus

    ... still remove the patch at your regular patch removal time. If it is almost time for the ... room temperature and away from excess heat and moisture (not in the bathroom). Throw away any patches ...

  5. Granisetron Transdermal Patch

    MedlinePlus

    ... the patch. Each patch is stuck onto a thin plastic liner and a separate rigid plastic film. Do not open the pouch in advance, because ... to cut the patch into pieces. Peel the thin plastic liner off of the printed side ... one piece of the plastic film from the sticky side of the patch. Be ...

  6. Scopolamine Transdermal Patch

    MedlinePlus

    ... patch from its protective pouch. To expose the adhesive surface of the patch, the clear plastic protective ... peeled off and discarded. Contact with the exposed adhesive layer should be avoided to prevent contamination of ...

  7. Lidocaine Transdermal Patch

    MedlinePlus

    ... that area. Use scissors to remove the outer seal from the package. Then pull apart the zipper seal. Remove up to three patches from the package and press the zipper seal tightly together. The remaining patches may dry out ...

  8. Diclofenac Transdermal Patch

    MedlinePlus

    ... and making sure not to cut the zipper seal just below it. Pull apart the zipper seal on the envelope and remove one patch. Reseal the envelope by squeezing the zipper seal together. Make sure the envelope is closed tightly ...

  9. Lidocaine Transdermal Patch

    MedlinePlus

    ... patches are used to relieve the pain of post-herpetic neuralgia (PHN; the burning, stabbing pains, or ... in your eye, wash it with plenty of water or saline solution. Wash your hands after handling ...

  10. Nicotine Transdermal Patch

    MedlinePlus

    ... patches are used to help people stop smoking cigarettes. They provide a source of nicotine that reduces ... cause harm to the fetus.do not smoke cigarettes or use other nicotine products while using nicotine ...

  11. Methylphenidate Transdermal Patch

    MedlinePlus

    ... for ADHD, which may include counseling and special education. Make sure to follow all of your doctor's ... that was covered by the patch seizures motion tics or verbal tics believing things that are not ...

  12. Nitroglycerin Transdermal Patch

    MedlinePlus

    ... verapamil (Calan, Isoptin); ergot-type medications such as bromocriptine (Parlodel), cabergoline, dihydroergotamine (D.H.E. 45, Migranal), ... at any time, especially if you have been drinking alcoholic beverages. To ... during your treatment with nitroglycerin patches.you should know that you ...

  13. [Use of Transdermal Fentanyl in a Hospital].

    PubMed

    Sako, Azumi; Yoshikawa, Yuka; Kikuchi, Norihiro; Watanabe, Atsuko; Yoshida, Seiya

    2016-03-01

    Recently, the use of transdermal fentanyl (TDF) has been increasing at our hospital owing to its convenience. Furthermore, TDF tends to be increasingly used for patients who have never used opioids. However, the appropriate criteria for indicating TDF have not been established yet. Therefore, we examined how TDF was prescribed in practice and determined its effective dosage. In 43 cases, the reasons, effects, and side effects of TDF were investigated retrospectively. Of the patients, 60% continued using TDF for 30 days. Meanwhile, approximately 25% of them terminated TDF therapy within 8 days. Of those who discontinued TDF therapy, some entirely stopped taking TDF and others chose other opioids instead because of poor pain control. Before receiving TDF therapy, 17 patients (45%) used oxycodone and 14 (37%) never used opioids. In addition, the main reason for starting TDF in opioid-naive patients was gastrointestinal condition. Between opioid-naive and opioid-using groups, no significant differences were observed in usage duration and incidence of side effects. The side effects included somnolence in 6 patients, delirium in 2 patients, and nausea and vomiting, constipation, and breathing restraint in 1 patient each. TDF was considered as an effective treatment regardless of the previous use of opioids. Nonetheless, careful deliberation is necessary because of the slow effects and difficulty with dosage adjustment. PMID:27067851

  14. Transdermal patches: history, development and pharmacology

    PubMed Central

    Pastore, Michael N; Kalia, Yogeshvar N; Horstmann, Michael; Roberts, Michael S

    2015-01-01

    Transdermal patches are now widely used as cosmetic, topical and transdermal delivery systems. These patches represent a key outcome from the growth in skin science, technology and expertise developed through trial and error, clinical observation and evidence-based studies that date back to the first existing human records. This review begins with the earliest topical therapies and traces topical delivery to the present-day transdermal patches, describing along the way the initial trials, devices and drug delivery systems that underpin current transdermal patches and their actives. This is followed by consideration of the evolution in the various patch designs and their limitations as well as requirements for actives to be used for transdermal delivery. The properties of and issues associated with the use of currently marketed products, such as variability, safety and regulatory aspects, are then described. The review concludes by examining future prospects for transdermal patches and drug delivery systems, such as the combination of active delivery systems with patches, minimally invasive microneedle patches and cutaneous solutions, including metered-dose systems. PMID:25560046

  15. Comparison between Transdermal Buprenorphine and Transdermal Fentanyl for Postoperative Pain Relief after Major Abdominal Surgeries

    PubMed Central

    Arshad, Zia; Gautam, Shefali; Kumar, Sanjeev

    2015-01-01

    Introduction Opioid is generally regarded as an important part of multimodal, perioperative analgesia, especially for moderate to severe pain. Amongst the various modes of delivery transdermal route has several potential benefits over oral and parentral administration. These include noninvasive dosing, better absorption and lack of first-pass metabolism. A transdermal drug delivery system provides steady and continuous drug delivery resulting in steady plasma concentration. Bolus dosing of systemic analgesic results in supra and sub therapeutic plasma resulting in toxic and sub analgesic plasma drug concentration. It also improves patient compliance. Materials and Methods Sixty patients undergoing major abdominal surgery under GA were randomly divided in two groups (n=30). Group A received buprenorphine 10 mcg/h TDS and group B received 25 mcg/h fentanyl TDS, 6 hours prior to surgery. Patients were followed for three days for postoperative pain relief and adverse effects. Results Baseline and demographic variables are comparable in both groups. The mean level of VAS was significantly lower in group B as compared to group A at Day 1, 2 and 3. The mean level of sedation score was significantly lower in Group B than Group A. Haemodynamic variables in both groups (SBP, DBP and HR), shows comparable values in both groups and no significant difference was observed. Five out of 30 (16.7%) patients in group A required single dose of rescue analgesic while 0 out of 30 patients (0.00%) in group B required rescue analgesic. This difference in rescue analgesic requirement in not quiet statistically significant (p-value 0.0522). Twenty percent patient in fentanyl group and 16.7% patients in buprenorphine group experienced some adverse effects. Nausea and vomiting were main side effects of the drugs. The incidence of nausea and vomiting were 6.7% and 10% in buprenorphine and fentanyl group respectively. Conclusion Fentanyl and buprenorphine TDS were effective and safe in

  16. Postoperative pain management with transdermal fentanyl after forefoot surgery: a randomized, placebo-controlled study

    PubMed Central

    Merivirta, Riika; Pitkänen, Mikko; Alanen, Jouko; Haapoja, Elina; Koivisto, Mari; Kuusniemi, Kristiina

    2015-01-01

    Background Quality of life is decreased in patients with hallux valgus deformity, mainly because of pain. Significant improvement is usually achieved by surgery. However, postoperative pain can be moderate to severe for 2–3 days. The aim of the present study was to evaluate the use of transdermal fentanyl for postoperative pain management after forefoot surgery. Methods Sixty patients undergoing hallux valgus or hallux rigidus surgery were allocated to receive a patch delivering either fentanyl 12 μg/hour or placebo for postoperative pain. The consumption of rescue opioid oxycodone, the primary outcome measure, was evaluated daily until the fourth postoperative day. Total consumption of oxycodone during the study period was also assessed. Pain scores and possible adverse effects were evaluated every 6 hours during the first 24 hours and on the fourth postoperative day. Results The use of rescue opioid was low in both groups, the median (range) consumption of oxycodone being 10 (0–50) mg on the day of surgery (no difference between the groups, P=0.31) and 0 (0–35) mg thereafter. The total combined consumption was 10 (0–105) mg in the fentanyl group and 20 (0–70) mg in the placebo group (P=0.23). There were no statistically significant differences in pain scores or adverse effects between the groups. Conclusion As a part of multimodal analgesia with ibuprofen and acetaminophen, a patch delivering fentanyl 12 μg/hour did not significantly decrease the consumption of rescue opioid or pain scores after forefoot surgery. PMID:25653553

  17. Fentanyl Patch Can Be Deadly to Children

    MedlinePlus

    ... Kellie Taylor, PharmD., MPH, in FDA’s Division of Medication Error Prevention and Analysis, FDA is aware of 32 ... the fentanyl. Focusing on the prevention of medical errors, Taylor and colleagues at FDA ... ...

  18. Medication errors related to transdermal opioid patches: lessons from a regional incident reporting system

    PubMed Central

    2014-01-01

    Objective A few cases of adverse reactions linked to erroneous use of transdermal opioid patches have been reported in the literature. The aim of this study was to describe and characterize medication errors (MEs) associated with use of transdermal fentanyl and buprenorphine. Methods All events concerning transdermal opioid patches reported between 2004 and 2011 to a regional incident reporting system and assessed as MEs were scrutinized and characterized. MEs were defined as “a failure in the treatment process that leads to, or has the potential to lead to, harm to the patient”. Results In the study 151 MEs were identified. The three most common error types were wrong administration time 67 (44%), wrong dose 34 (23%), and omission of dose 20 (13%). Of all MEs, 118 (78%) occurred in the administration stage of the medication process. Harm was reported in 26 (17%) of the included cases, of which 2 (1%) were regarded as serious harm (nausea/vomiting and respiratory depression). Pain was the most common adverse reaction reported. Conclusions Of the reported MEs related to transdermal fentanyl and buprenorphine, most occurred during administration. Improved routines to ascertain correct and timely administration and educational interventions to reduce MEs for these drugs are warranted. PMID:24912424

  19. Management of cancer pain with transdermal fentanyl: phase IV trial, University of Iowa.

    PubMed

    Maves, T J; Barcellos, W A

    1992-04-01

    A multicenter study was conducted to determine the patient and physician acceptability of transdermal fentanyl in the management of cancer-related pain. In this study, 10 cancer patients at the University of Iowa received transdermal fentanyl after discontinuing their prior opioid analgesic; 7 patients completed questionnaires before and at 2 and 4 wk following transdermal fentanyl application. There was no significant difference in visual analogue scale scores for pain or mood. Verbal pain descriptor scores improved at 2 wk (P less than .05). There was a nonsignificant tendency toward increased depression and nausea; however, patients spent less time thinking about their illness and felt their cancer was less disruptive to their closest friends/relatives. Constipation, appetite, drowsiness, and concentration were not statistically different. Patients reported improved sleep habits at 2 wk (P less than .05) and tended to require less help with eating, dressing, washing, and using the bathroom. All patients completing the study chose to continue transdermal fentanyl for their cancer pain management. In summary, these data demonstrate the analgesic efficacy of the transdermal fentanyl system and suggest that some patients with cancer-related pain could benefit from its use. PMID:1517636

  20. Comparative acceptance of three transdermal nitroglycerin placebo patches.

    PubMed

    Rayment, C M; Kaul, A F; Garfield, J M

    1985-06-01

    Factors that might affect patient acceptance of transdermal drug-delivery system patches were evaluated in healthy volunteers using placebo patches. Placebo transdermal nitroglycerin patches (Transderm-Nitro 5 placebo, Ciba Pharmaceutical Company; Nitro-Dur 10 cm2 placebo, Key Pharmaceuticals; and Nitrodisc 5 placebo, Searle Laboratories) were supplied by the manufacturers. Eighty-two healthy subjects were randomly assigned to begin using one of the three brands of patches. Using a Latin-square crossover design, subjects applied each brand of patch daily for five days and crossed over to the other brands on study days 6 and 11. At the end of each study phase, subjects completed a written questionnaire designed to evaluate their overall acceptance of each brand of patch. A total of 80 subjects completed all three phases of the study. According to forced rank preference, 84% of subjects preferred the Ciba patch to one of the other two brands. Subjects judged the Ciba patch to be the easiest of the three brands to use and reported significantly fewer side effects and skin irritation while using the Ciba patch; they also preferred the size of the Ciba patch and experienced significantly fewer problems with adherence of the Ciba patch. A significant percentage of subjects indicated that they would prefer a transdermal patch over tablets or ointment. Most subjects preferred the Ciba patch over the Key patch or Searle patch. PMID:3925770

  1. Rotigotine Transdermal Patch: A Review in Restless Legs Syndrome.

    PubMed

    Garnock-Jones, Karly P

    2016-07-01

    Rotigotine transdermal patch (Leganto(®), Neupro(®)) is indicated for the treatment of restless legs syndrome (RLS); this article reviews the pharmacological properties of rotigotine transdermal patch and its clinical efficacy and tolerability in patients with RLS. The transdermal patch allows for a continuous, stable release of rotigotine (avoiding first-pass metabolism), which in turn leads to continuous receptor stimulation, believed to closely mimic physiological striatal dopamine receptor function. In short-term and 6-month studies, especially at the higher dosages of 2 and 3 mg/24 h, rotigotine transdermal patch was generally associated with a significantly greater improvement in IRLS total score and CGI-S total score than placebo, and rotigotine recipients were generally more likely to respond to treatment and enter remission. In noncomparative extension studies, efficacy was sustained for ≤5 years. Rotigotine transdermal patch is generally well tolerated, and appears to have a tolerability profile that is similar to that of other non-ergolinic dopamine-receptor agonists. The most common adverse events in clinical trials included application-site reactions, nausea, headache and asthenic conditions. The drug has a relatively low risk of clinically significant augmentation of restless legs syndrome symptoms. In conclusion, rotigotine transdermal patch offers continuous administration of the drug in a daily treatment, and is a useful treatment option in patients with RLS. PMID:27324269

  2. Fentanyl Patches to Supplement Ultrasound-Guided Nerve Blocks for Improving Pain Control After Foot and Ankle Surgery: A Prospective Study.

    PubMed

    Song, Jae-Hwang; Kang, Chan; Hwang, Deuk-Soo; Hwang, Jung-Mo; Shin, Byung-Kon

    2016-01-01

    The analgesic effects of preoperative ultrasound-guided nerve blocks wear off after about 12 hours, leaving some patients in substantial pain. Transdermal fentanyl concentrations peak at 12 to 24 hours after application and maintain this concentration for approximately 72 hours. We sought to determine whether combining the use of a transdermal fentanyl patch with either a sciatic or femoral-sciatic nerve block would improve pain control in patients undergoing foot and/or ankle surgery. Consecutive patients in the no-patch control group (n = 104) were enrolled from July 2011 to October 2011, and those in the treatment group (n = 232) were enrolled from November 2011 to May 2012 and received a transdermal patch (4.125 mg/7.5 cm(2) releasing 25 μg of fentanyl per hour) applied to their chest postoperatively. Pain was assessed using a visual analog scale at 6, 12, 24, and 48 hours after surgery. The primary outcome measure was the number of requests for additional postoperative pain medication. Additional postoperative analgesia was requested by 49 of the 104 control patients (47.1%) and 63 of the 232 treated patients (27.1%; p = .002). The mean pain scores were also lower in the treatment group, with a statistically significant difference (p < .05) at 12, 24, and 48 hours. Thus, patients receiving a fentanyl patch combined with an ultrasound-guided nerve block required less supplemental analgesia to maintain adequate pain control than did those receiving a nerve block alone. In conclusion, a fentanyl patch is a useful adjunct to an ultrasound-guided nerve block in foot and ankle surgery. PMID:26422649

  3. Hydrogel blends with adjustable properties as patches for transdermal delivery.

    PubMed

    Mazzitelli, Stefania; Pagano, Cinzia; Giusepponi, Danilo; Nastruzzi, Claudio; Perioli, Luana

    2013-09-15

    The effect of different preparation parameters were analyzed with respect to the rheological and pharmaceutical characteristics of hydrogel blend patches, as transdermal delivery formulation. Mixtures of pectin and gelatin were employed for the production of patches, with adjustable properties, following a two-step gelation procedure. The first gelation, a thermal one, is trigged by the presence of gelatin, whereas, the second gelation, an ionic one, is due to the formation of the typical egg box structure of pectin. In particular, the patch structural properties were assessed by oscillation stress sweep measurements which provided information concerning their viscolelastic properties. In addition, different modalities for drug loading were analyzed with respect to drug homogeneous distribution; testosterone was employed as model drug for transdermal administration. Finally, the performances of the produced transdermal patches were studied, in term of reproducibility and reliability, by determination of in vitro drug release profiles. PMID:23856160

  4. Dosing considerations with transdermal formulations of fentanyl and buprenorphine for the treatment of cancer pain

    PubMed Central

    Skaer, Tracy L

    2014-01-01

    Opioids continue to be first-line pharmacotherapy for patients suffering from cancer pain. Unfortunately, subtherapeutic dosage prescribing of pain medications remains common, and many cancer patients continue to suffer and experience diminished quality of life. A large variety of therapeutic options are available for cancer pain patients. Analgesic pharmacotherapy is based on the patient’s self-report of pain intensity and should be tailored to meet the requirements of each individual. Most, if not all, cancer pain patients will ultimately require modifications in their opioid pharmacotherapy. When changes in a patient’s medication regimen are needed, adequate pain control is best maintained through appropriate dosage conversion, scheduling immediate release medication for withdrawal prevention, and providing as needed dosing for breakthrough pain. Transdermal opioids are noninvasive, cause less constipation and sedation when compared to oral opioids, and may improve patient compliance. A relative potency of 100:1 is recommended when converting the patient from oral morphine to transdermal fentanyl. Based on the limited data available, there is significant interpatient variability with transdermal buprenorphine and equipotency recommendations from oral morphine of 75:1–110:1 have been suggested. Cancer patients may require larger transdermal buprenorphine doses to control their pain and may respond better to a more aggressive 75–100:1 potency ratio. This review outlines the prescribing of transdermal fentanyl and transdermal buprenorphine including how to safely and effectively convert to and use them for those with cancer pain. PMID:25170278

  5. Postoperative Pain Control with the Fentanyl Patch and Continuous Paravertebral Anesthetic Infusion after Posterior Occipitocervical Junction Surgery

    PubMed Central

    Sivakumar, Walavan; Karsy, Michael; Brock, Andrea

    2016-01-01

    Postoperative pain is a significant concern for patients who undergo surgery via a midline posterior approach to the occipitocervical junction and spinal axis. The development of the disposable, ambulatory pain pump presents a novel alternative for treatment of postoperative pain. The authors describe a multimodal treatment algorithm for postoperative pain after posterior occipitocervical junction surgery that uses the On-Q pain catheter system (I-Flow Corp., Lake Forest, CA) and a fentanyl patch. The On-Q PainBuster catheter system is a disposable, ambulatory device that allows for continuous anesthetic delivery directly into or adjacent to the wound. On-Q catheters are placed in the nuchal musculature for continuous infusion of 0.5% bupivacaine. The On-Q catheter infusion is continued for three days, and the catheters are then withdrawn. Patients are also provided with a transdermal fentanyl patch at the start of surgery. In regards to complications at our facility, there have been no cases of respiratory depression or arrest postoperatively and no wound infections, but one case of inadvertent subdural placement. The technique described for the use of the fentanyl patch and a continuous anesthetic delivery device in surgery of the occipitocervical junction presents a novel alternative to the current standard of care in pain control after suboccipital decompression. PMID:27433423

  6. Postoperative Pain Control with the Fentanyl Patch and Continuous Paravertebral Anesthetic Infusion after Posterior Occipitocervical Junction Surgery.

    PubMed

    Sivakumar, Walavan; Karsy, Michael; Brock, Andrea; Schmidt, Richard H

    2016-01-01

    Postoperative pain is a significant concern for patients who undergo surgery via a midline posterior approach to the occipitocervical junction and spinal axis. The development of the disposable, ambulatory pain pump presents a novel alternative for treatment of postoperative pain. The authors describe a multimodal treatment algorithm for postoperative pain after posterior occipitocervical junction surgery that uses the On-Q pain catheter system (I-Flow Corp., Lake Forest, CA) and a fentanyl patch. The On-Q PainBuster catheter system is a disposable, ambulatory device that allows for continuous anesthetic delivery directly into or adjacent to the wound. On-Q catheters are placed in the nuchal musculature for continuous infusion of 0.5% bupivacaine. The On-Q catheter infusion is continued for three days, and the catheters are then withdrawn. Patients are also provided with a transdermal fentanyl patch at the start of surgery. In regards to complications at our facility, there have been no cases of respiratory depression or arrest postoperatively and no wound infections, but one case of inadvertent subdural placement. The technique described for the use of the fentanyl patch and a continuous anesthetic delivery device in surgery of the occipitocervical junction presents a novel alternative to the current standard of care in pain control after suboccipital decompression. PMID:27433423

  7. Ethinyl Estradiol and Norelgestromin Transdermal Patch

    MedlinePlus

    ... the skin. One patch is applied once a week for 3 weeks, followed by a patch-free week. Follow the directions on your prescription label carefully, ... new patch on the same day of the week (the Patch Change Day). Apply a new patch ...

  8. Patient considerations in the use of transdermal iontophoretic fentanyl for acute postoperative pain

    PubMed Central

    Hartrick, Craig T; Pestano, Cecile R; Ding, Li; Danesi, Hassan; Jones, James B

    2016-01-01

    Opioids are commonly used in the management of moderate-to-severe postoperative pain. Patient-controlled analgesic techniques are recognized as preferred administration methods. Previously, research has focused on intravenously administered opioids via a programmable pump. More recently, an iontophoretic transdermal system (ITS), which is patient controlled, has been developed. The focus of this review is on pain management using the fentanyl ITS during the 24–72-hour time period immediately following surgery. Fentanyl ITS offers a needle-free alternative to traditional intravenous (IV) patient-controlled analgesia (PCA) system that is as effective and safe as IV PCA. This system is easy to use for both patients and nurses. The use of fentanyl ITS is generally associated with a better ease-of-care profile, including a greater ease of mobility, from a patients’ perspective when compared with morphine IV PCA. PMID:27186073

  9. Taro corms mucilage/HPMC based transdermal patch: an efficient device for delivery of diltiazem hydrochloride.

    PubMed

    Sarkar, Gunjan; Saha, Nayan Ranjan; Roy, Indranil; Bhattacharyya, Amartya; Bose, Madhura; Mishra, Roshnara; Rana, Dipak; Bhattacharjee, Debashis; Chattopadhyay, Dipankar

    2014-05-01

    The aim of this work is to examine the effectiveness of mucilage/hydroxypropylmethylcellulose (HPMC) based transdermal patch (matrix type) as a drug delivery device. We have successfully extracted mucilage from Colocasia esculenta (Taro) corms and prepared diltiazem hydrochloride incorporated mucilage/HPMC based transdermal patches using various wt% of mucilage by the solvent evaporation technique. Characterization of both mucilage and transdermal patches has been done by several techniques such as Molisch's test, organoleptic evaluation of mucilage, mechanical, morphological and thermal analysis of transdermal patches. Skin irritation test is studied on hairless Albino rat skin showing that transdermal patches are apparently free of potentially hazardous skin irritation. Fourier transform infrared analysis shows that there is no interaction between drug, mucilage and HPMC while scanning electron microscopy shows the surface morphology of transdermal patches. In vitro drug release time of mucilage-HPMC based transdermal patches is prolonged with increasing mucilage concentration in the formulation. PMID:24556117

  10. Patient-Controlled Transdermal Fentanyl Versus Intravenous Morphine Pump After Spine Surgery.

    PubMed

    Lindley, Emily M; Milligan, Kenneth; Farmer, Ryan; Burger, Evalina L; Patel, Vikas V

    2015-09-01

    Patient-controlled analgesia (PCA) is regularly used to manage pain following major surgery. The fentanyl hydrochloride iontophoretic transdermal system (ITS) was developed to overcome some of the limitations of intravenous (IV) PCA. The small, self-adhesive, needle-free disposable system is applied to the skin on the upper arm or chest and is controlled by patients clicking a button on the device. The authors identified patients who were underwent spinal surgery from 2 prior multicenter, randomized studies and analyzed their data. Of the 1296 patients in the original trials, 170 underwent spine surgery procedures: 90 were randomized to the fentanyl ITS (40 mcg/activation) and 80 to IV PCA morphine (1 mg/dose). More patients treated with the fentanyl ITS rated their method of pain control as "excellent" across all time points, but differences did not reach statistical significance. However, investigators' ratings of "excellent" satisfaction with study treatment were significantly higher for the fentanyl ITS. Discontinuation rates and overall adverse event rates were similar between groups. The only significant difference was that patients treated with the fentanyl ITS had a higher rate of application site reactions than infusion site reactions in the IV PCA morphine group; the reactions were typically mild-to-moderate erythema that resolved shortly after removal of the fentanyl ITS device and did not require further treatment. Ratings of satisfaction with pain control method were consistently higher for the fentanyl ITS than the IV PCA morphine. The 2 groups had a similar safety profile. These results suggest that the fentanyl ITS appears to be a safe, efficacious alternative to IV PCA in spine surgery patients. PMID:26375541

  11. Transdermal Buprenorphine Patches for Postoperative Pain Control in Abdominal Surgery

    PubMed Central

    Kumar, Santosh; Singh, Prithvi Kumar; Verma, Reetu; Chandra, Girish; Bhatia, Vinod Kumar; Singh, Dinesh; Bogra, Jaishri

    2016-01-01

    Introduction Buprenorphine is a semi-synthetic derivative of thebaine; its low concentration is sufficient to provide effective pain relief. Aim To evaluate the efficacy of transdermal buprenorphine patch in postoperative pain management. Materials and Methods After ethical approval and taking informed consent from the patients, they were randomized into three groups (n=30 in each group) using a computer generated random number table. Group A: placebo patch; Group B: buprenorphine (10mg) patch and Group C: buprenorphine (20mg) patch. Haemodynamic and analgesic effects were compared by using analysis of variance (ANOVA) followed by Turkey’s post hoc test. The proportion of side effects was compared using the Chi-square test. Results Haemodynamic changes were not statistically different in all the three groups A, B and C, whereas at the end of surgery VAS score of Group A subjects was significantly higher (4.93±0.98) as compared to Group B (1.73±0.64) and Group C (1.40±0.50). On 2nd postoperative day, no pain was reported by the Group C patients and on 4th day after surgery, no pain was reported by Group B patients. Conclusion The transdermal buprenorphine patch (20mg) was effective in attenuating postoperative pain, maintaining haemodynamic stability requiring no rescue analgesia, with fewer postoperative rescue analgesic requirements in low dose of buprenorphine patch (10mg) group. PMID:27504383

  12. Ethinyl Estradiol and Norelgestromin Transdermal Patch

    MedlinePlus

    ... contraceptive patch is a very effective method of birth control, but it does not prevent the spread of ... period, you must use a backup method of birth control (such as a condom and/or a spermicide) ...

  13. Pain Management in the Elderly: Transdermal Fentanyl for the Treatment of Pain Caused by Osteoarthritis of the Knee and Hip

    PubMed Central

    2014-01-01

    This study was designed to evaluate the utility of transdermal fentanyl (transdermal fentanyl, TDF) for the treatment of pain due to osteoarthritis (osteoarthritis, OA) of the knee and hip, which was not adequately controlled by nonopioid analgesics or weak opioids. WOMAC is a reliable, valid, and responsive multidimensional, self-administrated outcome measure designed specifically to evaluate patients with OA of the knee or hip. TDF significantly increased pain control and improved functioning and quality of life. Metoclopramide appeared to be of limited value in preventing nausea and vomiting. PMID:24527441

  14. Formulation development and investigation of domperidone transdermal patches

    PubMed Central

    Prabhu, Prabhakar; Shah, Samip; Gundad, Shankar

    2011-01-01

    Aim and Background: Domperidone is a dopamine antagonist with antiemetic properties having a plasma half life of 7-9 h with 15% oral bioavailability. In the present work transdermal patches of domperidone were prepared with the objective to improve its therapeutic efficacy, patient compliance and to reduce the frequency of dosing and side effects, as well as to avoid its extensive first pass metabolism of the drug. Materials and Methods: The patches were prepared using ethyl cellulose (EC): Poly vinyl pyrrolidone (PVP), poly vinyl alcohol (PVA): Poly vinyl pyrrolidone (PVP) and hydroxypropylmethylcellulose (HPMC): Sodium (carboxy methyl cellulose) CMC as polymers in combination. The physicochemical parameters like thickness, drug content, weight variation, moisture absorption and drug permeation studies were evaluated for the prepared patches. No significant difference in thickness, average weight and in the drug content among the patches. Results: It was observed that from hydrophilic polymers the drug release was found to be faster compared to (F5 and F6 & F3 and F4) combination of hydrophilic and lipophilic polymers used in the study. Patches containing HPMC and Sodium CMC (F5 and F6) showed faster release as the patches showed maximum percentage amount moisture absorption. The in vitro release data was treated with kinetic equations and it followed Higuchi's diffusion mechanism. The in vivo bioavailability study was performed in rats and observed that, drug reached to the peak in approximately 60 min (16%) after oral route of administration. However, approximately same amount of drug was found in the serum from transdermal formulation in 6 h and further increase in the amount of drug in the serum, indicated that the drug 5 bioavailability could be better and hence the hepatic metabolism can be avoided, as it is evident from the data. Further, the decrease in the amount of drug present in the serum 45 min after oral administration also indicated that major

  15. The effect of transdermal nicotine patches on sleep and dreams.

    PubMed

    Page, F; Coleman, G; Conduit, R

    2006-07-30

    This study was undertaken to determine the effect of 24-h transdermal nicotine patches on sleep and dream mentation in 15 smokers aged 20 to 33. Utilising a repeated measures design, it was found that more time awake and more ASDA micro-arousals occurred while wearing the nicotine patch compared to placebo. Also, the percentage of REM sleep decreased, but REM latency and the proportion of time spent in NREM sleep stages did not change significantly. Dream reports containing visual imagery, visual imagery ratings and the number of visualizable nouns were significantly greater from REM compared to Stage 2 awakenings, regardless of patch condition. However, a general interaction effect was observed. Stage 2 dream variables remained equivalent across nicotine and placebo conditions. Within REM sleep, more dream reports containing visual imagery occurred while wearing the nicotine patch, and these were rated as more vivid. The greater frequency of visual imagery reports and higher imagery ratings specifically from REM sleep suggests that previously reported dreaming side effects from 24-h nicotine patches may be specific to REM sleep. Combined with previous animal studies showing that transdermally delivered nicotine blocks PGO activity in REM sleep, the current results do no appear consistent with PGO-based hypotheses of dreaming, such as the Activation-Synthesis (AS) or Activation, Input and Modulation (AIM) models. PMID:16782142

  16. Design and functionality of a smart fentanyl iontophoretic transdermal system for the treatment of moderate-to-severe postoperative pain.

    PubMed

    Joshi, Nitin; Lemke, John; Danesi, Hassan

    2016-04-01

    Fentanyl iontophoretic transdermal system (ITS) is a patient-controlled analgesia system used for the management of acute postoperative pain. The first-generation fentanyl ITS was an integrated one-piece system; however, corrosion that could limit reliability was detected in a small number of systems. A second-generation fentanyl ITS was designed to separate the hydrogels in the Drug Unit from the electronic circuit of the Controller during manufacture and storage, removing the primary cause of corrosion and thereby improving reliability. No evidence of corrosion has been observed in over 10,000 systems tested in real-time aging studies for the second generation fentanyl ITS. The second generation fentanyl ITS design features combine to ensure safe operation of the system with high reliability. PMID:26805009

  17. Transdermal opioid patches for pain treatment in ancient Greece.

    PubMed

    Harrison, Adrian P; Hansen, Steen H; Bartels, Else M

    2012-11-01

    Pain treatment in ancient Greece, and through the middle ages in Europe, was to a great extent based on the expertise of the Greek physician Galen (c. 129-200 A.D.). Galen makes particular reference to "Olympic Victor's Dark Ointment" (OVDO), which is listed with a number of collyria. Galen states that OVDO can be useful for treating extreme pain and swellings, forming one of the best eye salves. Olympic Victor's Dark Ointment, an opium-based treatment, forms a "patch" when applied externally as an ointment, because it quickly dries to cover a localized region but still retains its elastic properties. This study has recreated OVDO and applied the ointment to abdominal mouse skin, in vitro. To assess the efficacy of OVDO, the transdermal transfer of morphine was measured when given as OVDO and compared to morphine administered in the form of a solution of Opium + PBS (ringer). Olympic Victor's Dark Ointment showed a transdermal transfer of morphine over time comparable to 25% of the most efficient modern transdermal opioid patches, while hardly any morphine was able to penetrate the skin when applied mixed in PBS. We conclude that OVDO is very efficient in its composition and may carry some forgotten abilities in terms of drug delivery, which could be transferred to modern medicine. Indeed, this may lead to a better choice of morphine use and controlled management in individual patient cases, taking both pain relief and anti-inflammatory aspects into account. PMID:22448887

  18. PHARMACOKINETIC EVALUATION OF A LONG-ACTING FENTANYL SOLUTION AFTER TRANSDERMAL ADMINISTRATION IN HELMETED GUINEAFOWL (NUMIDA MELEAGRIS).

    PubMed

    Waugh, Lynnette; Knych, Heather; Cole, Gretchen; D'Agostino, Jennifer

    2016-06-01

    The objective of this study was to investigate the pharmacokinetics of a long-acting fentanyl solution in helmeted guineafowl ( Numida meleagris ) after transdermal administration. Twenty-one guineafowl received a single administration of 5 mg/kg of fentanyl transdermal solution. No adverse effects on behavior were appreciated. Plasma fentanyl concentrations were determined by liquid chromatography-mass spectrometry analysis of protein-precipitated samples. Mean maximum plasma concentration was 228.8 ng/ml at 4 hr. The mean plasma terminal half-life was 33.2 hr. At 168 hr the mean plasma concentration was 1.3 ng/ml. A single topical dose of 5 mg/kg appears to be safe for use in this species and maintained plasma concentrations above those reported to be analgesic in dogs for at least 7 days. PMID:27468018

  19. [Continued Use of Rotigotine Transdermal Patches for Parkinson Disease].

    PubMed

    Yasutaka, Yuki; Fujioka, Shinsuke; Shibaguchi, Hirotomo; Imakyure, Osamu; Washiyama, Atsushi; Tsuboi, Yoshio; Futagami, Koujiro

    2016-06-01

    Transdermal patches containing rotigotine, a dopamine agonist (DA) for treatment of Parkinson disease, continuously exert stable effects when applied once daily. Therefore, they are expected to reduce the patient burdens due to complications such as wearing-off and dysphagia. However, dosing is occasionally reduced or discontinued after application because of several reasons such as skin reactions or unsatisfactory efficacy. To identify the risk factors involved in the reduced or discontinued use of rotigotine patches, a retrospective study was conducted with reference to the medical records of patients with Parkinson disease who received rotigotine patches in our hospital. 85 patients were involved in this study. Dosing of rotigotine was reduced or discontinued in 53 patients during the study period. The factors associated with charges in treatment included combination therapy with clonazepam and oral administration of another DA before the application of rotigotine. The reduction or discontinuation rate of rotigotine patches in patients who reduced the equivalent dose of DA on the introduction of rotigotine patches was 94.7%, showing a significantly higher rate compared with 61.3% in the increased dose group. To improve adherence to rotigotine patch therapy, physicians need to carefully consider concomitant drugs and total dose of DAs. (Received December 7, 2015; Accepted February 22, 2016; Published June 1, 2016). PMID:27279164

  20. Fentanyl

    MedlinePlus

    ... Trends and Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Prescription ... Street names for fentanyl or for fentanyl-laced heroin include Apache, China Girl, China White, Dance Fever, ...

  1. Fentanyl

    MedlinePlus

    ... a sublingual (underneath the tongue) tablet (Abstral), a film (Onsolis), and a buccal (between the gum and ... still have pain 30 minutes after using fentanyl films (Onsolis), your doctor may tell you to use ...

  2. Innate Immune Signalling Genetics of Pain, Cognitive Dysfunction and Sickness Symptoms in Cancer Pain Patients Treated with Transdermal Fentanyl

    PubMed Central

    Barratt, Daniel T.; Klepstad, Pål; Dale, Ola; Kaasa, Stein; Somogyi, Andrew A.

    2015-01-01

    Common adverse symptoms of cancer and chemotherapy are a major health burden; chief among these is pain, with opioids including transdermal fentanyl the mainstay of treatment. Innate immune activation has been implicated generally in pain, opioid analgesia, cognitive dysfunction, and sickness type symptoms reported by cancer patients. We aimed to determine if genetic polymorphisms in neuroimmune activation pathways alter the serum fentanyl concentration-response relationships for pain control, cognitive dysfunction, and other adverse symptoms, in cancer pain patients. Cancer pain patients (468) receiving transdermal fentanyl were genotyped for 31 single nucleotide polymorphisms in 19 genes: CASP1, BDNF, CRP, LY96, IL6, IL1B, TGFB1, TNF, IL10, IL2, TLR2, TLR4, MYD88, IL6R, OPRM1, ARRB2, COMT, STAT6 and ABCB1. Lasso and backward stepwise generalised linear regression were used to identify non-genetic and genetic predictors, respectively, of pain control (average Brief Pain Inventory < 4), cognitive dysfunction (Mini-Mental State Examination ≤ 23), sickness response and opioid adverse event complaint. Serum fentanyl concentrations did not predict between-patient variability in these outcomes, nor did genetic factors predict pain control, sickness response or opioid adverse event complaint. Carriers of the MYD88 rs6853 variant were half as likely to have cognitive dysfunction (11/111) than wild-type patients (69/325), with a relative risk of 0.45 (95% CI: 0.27 to 0.76) when accounting for major non-genetic predictors (age, Karnofsky functional score). This supports the involvement of innate immune signalling in cognitive dysfunction, and identifies MyD88 signalling pathways as a potential focus for predicting and reducing the burden of cognitive dysfunction in cancer pain patients. PMID:26332828

  3. Fentanyl

    MedlinePlus

    ... spit the remaining pieces of tablet into the sink or toilet. Flush the toilet or rinse the sink to wash away the tablet pieces. To use ... fentanyl at room temperature and away from excess heat and moisture (not in the bathroom). Do not ...

  4. In vitro evaluation of transdermal patches of flurbiprofen with ethyl cellulose.

    PubMed

    Idrees, Arfat; Rahman, Nisar Ur; Javaid, Zeeshan; Kashif, Muhammad; Aslam, Irfan; Abbas, Khizar; Hussain, Talib

    2014-01-01

    This study was aimed to determine effects of penetration enhancers and plasticizers on drug release from rationally designed formulations of flurbiprofen based transdermal drug delivery system. Matrix type transdermal patches were formulated with ethyl cellulose (EC) as a polymer by using plate casting method. The plasticizers such as propylene glycol (PG) and dibutyl phthalate (DBP), and enhancers such as Span 20, Tween 20, sodium lauryl sulfate (SLS), isopropyl myristate (IPM) and ethanol (EtOH) were formulated in different concentrations in the patches. Such different combinations of polymer with various enhancers and plasticizers in patches were evaluated for their effect on the physicochemical properties and drug release behavior of flurbiprofen. The drug release study was carried out by the paddle-over-disk method and permeation of drug was performed by Franz diffusion cell using rabbit skin. Patches having ethanol with ethyl cellulose showed more uniformity in the physical properties while the smoothness and clarity of patches containing sodium lauryl sulfate were not satisfactory. The drug release from patches followed Higuchi and Korsmeyer-Pappas model while maximum drug release was obtained by isopropyl myristate (903 microg). It was concluded that the patches having ethyl cellulose with isopropyl myristate and propylene glycol are more useful for transdermal patches of flurbiprofen. PMID:25272649

  5. Synthesis of Conjugated Chitosan and its Effect on Drug Permeation from Transdermal Patches

    PubMed Central

    Satheeshababu, B. K.; Shivakumar, K. L.

    2013-01-01

    The aim of this study was to synthesis the conjugated chitosan by covalent attachment of thiol moieties to the cationic polymer, mediated by a carbodiimide to improve permeation properties of chitosan. Thioglycolic acid was covalently attached to chitosan by the formation of amide bonds between the primary amino groups of the polymer and the carboxylic acid groups of thioglycolic acid. Hence, these polymers are called as thiomers or thiolated polymers. Conjugation of chitosan was confirmed by Fourier transform-infrared and differential scanning calorimetric analysis. Matrix type transdermal patches of carvedilol were prepared using the different proportions of chitosan and chitosan-thioglycolic acid conjugates (2:0, 1.7:0.3, 1.4:0.6, 1:1, 0.6:1.4 and 0.3:1.7) by solvent casting technique. Prepared matrix type patches were evaluated for their physicochemical characterization followed by in vitro evaluation. Selected formulations were subjected for their ex vivo studies on Wistar albino rat skin and human cadaver skin using the modified Franz diffusion cell. As the proportion of conjugated chitosan increased, the transdermal patches showed increased drug permeation. The mechanism of drug release was found to be nonFickian profiles. The present study concludes that the transdermal patches of carvedilol using conjugated chitosan with different proportions of chitosan were successfully developed to provide improved drug permeation. The transdermal patches can be a good approach to improve drug bioavailability by bypassing the extensive hepatic first-pass metabolism of the drug. PMID:24019564

  6. Formulation and Evaluation of Galantamine Gel as Drug Reservoir in Transdermal Patch Delivery System

    PubMed Central

    Fong Yen, Woo; Basri, Mahiran; Ahmad, Mansor; Ismail, Maznah

    2015-01-01

    Galantamine hydrobromide is formulated in tablets and capsules prescribed through oral delivery for the treatment of Alzheimer's disease. However, oral delivery of drugs can cause severe side effects such as nausea, vomiting, and gastrointestinal disturbance. Transdermal delivery of galantamine hydrobromide could avoid these unwanted side effects. In this work, galantamine hydrobromide was formulated in gel drug reservoir which was then fabricated in the transdermal patch. The in vitro drug release studies revealed that the drug release from the donor chamber to receptor chamber of Franz diffusion cell was affected by the amount of polymer, amount of neutralizer, amount of drug, types of permeation enhancer, and amount of permeation enhancer. Visual observations of the gels showed that all formulated gels are translucent, homogeneous, smooth, and stable. These gels have pH in the suitable range for skin. The gel also showed high drug content uniformity. Hence, this formulation can be further used in the preparation of transdermal patch drug delivery system. PMID:25853145

  7. Effects of Internet-Based Voucher Reinforcement and a Transdermal Nicotine Patch on Cigarette Smoking

    ERIC Educational Resources Information Center

    Glenn, Irene M.; Dallery, Jesse

    2007-01-01

    Nicotine replacement products are commonly used to promote smoking cessation, but alternative and complementary methods may increase cessation rates. The current experiment compared the short-term effects of a transdermal nicotine patch to voucher-based reinforcement of smoking abstinence on cigarette smoking. Fourteen heavy smokers (7 men and 7…

  8. Effects of Internet-Based Voucher Reinforcement and a Transdermal Nicotine Patch on Cigarette Smoking

    PubMed Central

    Glenn, Irene M; Dallery, Jesse

    2007-01-01

    Nicotine replacement products are commonly used to promote smoking cessation, but alternative and complementary methods may increase cessation rates. The current experiment compared the short-term effects of a transdermal nicotine patch to voucher-based reinforcement of smoking abstinence on cigarette smoking. Fourteen heavy smokers (7 men and 7 women) completed the four 5-day phases of the study: baseline, patch treatment, voucher treatment, and return to baseline. The order of the two treatment phases was counterbalanced across participants. In the patch treatment condition, participants wore a 14-mg transdermal nicotine patch every day. In the voucher treatment condition, participants received vouchers contingent on abstinence from smoking, defined as producing carbon monoxide (CO) readings of ≤4 parts per million. Participants e-mailed two video clips per day showing them breathing into a CO monitor and the resulting CO reading to clinic staff. In the voucher treatment, 24% of samples were negative, and 5% of samples were negative in the patch treatment. Results suggest that contingent vouchers were more effective than transdermal nicotine patches in promoting abstinence. PMID:17471790

  9. Hydrogel patches for transdermal drug delivery; in-vivo water exchange and skin compatibility.

    PubMed

    Boddé, H E; Van Aalten, E A; Junginger, H E

    1989-03-01

    Hydrogel patches based on water swellable polyacrylates have been developed for long-term transdermal drug delivery. Two properties, relevant to the performance of hydrogel patches in-vivo have been investigated in humans over five days. These were: (i) the kinetics of water exchange between the skin and the patches; (ii) the skin compatibility of the patches. It was found that initially there was a gradually increasing uptake of water from the skin by the patches, but after about 20 h the water exchange followed a regular fluctuating pattern, peaking once a day and once a night. The skin compatibility of the patches was satisfactory, in that no redness or pustulation was noticed throughout the five days. This was most likely due to the capability of the patches to exchange water with the skin. PMID:2568439

  10. Formulation, in vitro, and in vivo evaluation of matrix-type transdermal patches containing olanzapine.

    PubMed

    Aggarwal, Geeta; Dhawan, Sanju; Harikumar, S L

    2013-01-01

    Transdermal patches of olanzapine were aimed to be prepared to overcome the side effects by oral application. The strategy was formulation of eudragit-based polymeric films to prepare transdermal patches by using nonionic (span-20), anionic (sodium lauryl sulfate), cationic surfactant (benzalkonium chloride), and vegetable oil (olive oil) as permeation enhancers. The patches were subjected to physicochemical, in vitro release and ex vivo permeation studies. On the basis of in vitro release performance, ERL 100:ERS 100 in the ratio of 3:2 was selected for incorporation of permeation enhancers. The permeation studies showed that formulation containing 10% span 20 (OD3) exhibited greatest cumulative amount of drug permeated (19.02 ± 0.21 mg) in 72 h, so OD3 was concluded as optimized formulation and assessed for pharmacokinetic, pharmacodynamic, and skin irritation potential. In vivo studies of optimized olanzapine patch in rabbit model revealed prolongation of action with Frel 116.09% during 72-h study period. Neuroleptic efficacy of transdermal patch was comparable to oral formulation during rotarod and grip test in Wistar albino rats with no skin irritation. Thus, developed formulation of olanzapine is expected to improve the patient compliance, form better dosage regimen, and provide maintenance therapy to psychotic patients. PMID:21913873

  11. Formulation Design and Development of a Unani Transdermal Patch for Antiemetic Therapy and Its Pharmaceutical Evaluation

    PubMed Central

    Idris, Mohammad

    2016-01-01

    The Transdermal Drug Delivery System (TDDS) is one of the novel routes for systemic delivery of drugs through intact skin. A transdermal patch (TP) is a medicated patch that is placed on skin for delivery of medication through skin into the blood stream. The aim of present study was to formulate and evaluate a Unani transdermal patch that could be used for antiemetic therapy. The incorporation of Unani ingredients, namely, Khardal (Brassica nigra), Zanjabeel (Zingiber officinale), Podina (Mentha arvensis), and Sirka (Vinegar) were envisaged. The TP was prepared by solvent evaporation technique and was evaluated for organoleptic characteristics and other physicochemical properties, such as thickness, weight uniformity, folding endurance, moisture content, drug content, and tolerability and acceptability of patch. The in vitro permeation study of the patch was carried out through Franz diffusion cell using egg shell membrane as barrier membrane. Phosphate buffer pH 7.4 was used as dissolution medium and the temperature was maintained at 37 ± 1°C. The in vitro permeation study of the prepared TP indicated a time dependent increase in drug release throughout the study. The percentage of cumulative drug release was found to be 77.38% in 24 hours. The study shows a new approach to work in Unani pharmaceutics. PMID:27403377

  12. Formulation Design and Development of a Unani Transdermal Patch for Antiemetic Therapy and Its Pharmaceutical Evaluation.

    PubMed

    Saleem, Mohd Nauman; Idris, Mohammad

    2016-01-01

    The Transdermal Drug Delivery System (TDDS) is one of the novel routes for systemic delivery of drugs through intact skin. A transdermal patch (TP) is a medicated patch that is placed on skin for delivery of medication through skin into the blood stream. The aim of present study was to formulate and evaluate a Unani transdermal patch that could be used for antiemetic therapy. The incorporation of Unani ingredients, namely, Khardal (Brassica nigra), Zanjabeel (Zingiber officinale), Podina (Mentha arvensis), and Sirka (Vinegar) were envisaged. The TP was prepared by solvent evaporation technique and was evaluated for organoleptic characteristics and other physicochemical properties, such as thickness, weight uniformity, folding endurance, moisture content, drug content, and tolerability and acceptability of patch. The in vitro permeation study of the patch was carried out through Franz diffusion cell using egg shell membrane as barrier membrane. Phosphate buffer pH 7.4 was used as dissolution medium and the temperature was maintained at 37 ± 1°C. The in vitro permeation study of the prepared TP indicated a time dependent increase in drug release throughout the study. The percentage of cumulative drug release was found to be 77.38% in 24 hours. The study shows a new approach to work in Unani pharmaceutics. PMID:27403377

  13. Designing and characterizing of tramadol hydrochloride transdermal patches prepared with Ficus carica fruit mucilage and povidone.

    PubMed

    Ahad, Hindustan Abdul; Ishaq, Beludari Mohammed; Shaik, Muneer; Bandagisa, Faheem

    2016-05-01

    The purpose of this investigation was to prepare matrix type transdermal patches of Tramadol HCl using various ratios of Ficus carica fruit mucilage and Povidone. The matrix type transdermal patches were prepared using Tramadol HCl with Ficus carica fruit mucilage and Povidone. The interactions between Tramadol HCl with F. carica fruit mucilage and Povidone were performed by Differential Scanning Calorimetry (DSC) and Fourier Transform Infrared spectroscopy (FTIR). The prepared patches were examined for physicochemical characterization and in vitro drug permeation studies (using a Keshary-Chien diffusion cell across hairless Albino rat skin), skin irritation studies and accelerated stability studies. The drug was found to be free from negligible interactions with the polymers used. The formulated patches possessed satisfactory physicochemical properties, in vitro drug permeation and devoid of serious skin irritation. The selected formulation (F-5) was retains the characteristics even after the accelerated environmental conditions. The study concludes that F. carica fruit mucilage with Povidone is a good combination for preparing transdermal patches. PMID:27166538

  14. Transdermal nicotine patches do not cause clinically significant gastroesophageal reflux or esophageal motor disorders.

    PubMed

    Wright, R A; Goldsmith, L J; Ameen, V; D'Angelo, A; Kirby, S L; Prakash, S

    1999-12-01

    Transdermal nicotine delivery systems are widely used in smoking cessation. The purpose of this study was to determine whether common symptoms of pyrosis and dyspepsia associated with these patches are related to gastroesophageal reflux or esophageal dysmotility. Twenty-seven paid volunteer cigarette smokers (> 15 cigarettes/day) without symptomatic gastroesophageal reflux disease participated in this single-blinded, placebo-controlled study. Twenty subjects completed the study. Subjects underwent three sequential 24-h intraesophageal pH/motor studies (Synectics model T32342084, Shore View, MN). The pH/motility probe was positioned 5 cm above the manometrically determined LES. A placebo patch was applied for the first 24-h study and a 15-mg nicotine patch (Nicotrol) was applied for the initial 16 h (removed for remaining 8 h) of the second 24-h period. A 21-mg nicotine patch (Nicoderm) was applied for another 24-h study period. All subjects consumed an identical, defined diet documented by meal receipts, and refrained from smoking and tobacco use throughout the study periods (CO breath test confirmation). The Wilcoxon, paired t-test, exact McNemar statistical methods were used. The results showed that there were no significant differences in reflux symptoms (pyrosis, chest pain, nausea, dysphagia), supine gastroesophageal reflux (number of episodes, duration, or cumulative acid exposure), or the total number of reflux episodes between placebo and nicotine patch treatment periods. The number of post-prandial upright acid reflux episodes (p = 004) and number of upright acid reflux episodes lasting more than 5 min (p = 0.007) were statistically higher with the placebo patch compared to the active nicotine patches. No differences in intraesophageal pH or motility indices were noted between the two transdermal nicotine patches (Nicotrol, Nicoderm). It was concluded that dyspeptic symptoms in subjects utilizing transdermal nicotine patches are not related to

  15. Switching From Oral Donepezil to Rivastigmine Transdermal Patch in Alzheimer's Disease: 20-Week Extension Phase Results

    PubMed Central

    Dengiz, Alan; Meng, Xiangyi; Olin, Jason T.

    2010-01-01

    Objective: To evaluate the long-term safety, tolerability, and efficacy of 2 strategies for switching from donepezil to rivastigmine transdermal patches in patients with mild to moderate Alzheimer's disease. Method: This was a prospective, 25-week, randomized, open-label, parallel-group study to evaluate an immediate or delayed switch (7-day withdrawal) from donepezil (5 to 10 mg/d) to rivastigmine transdermal patches (4.6 mg/24 h). Participants included male and female patients, aged ≥ 50 years, with a DSM-IV-TR diagnosis of mild to moderate dementia of the Alzheimer's type, defined as a Mini-Mental State Examination score of 10–24, inclusive. Patients were enrolled between February 2007 and February 2008. The study was split into a 5-week core phase and a 20-week extension phase. Safety and efficacy results from the extension phase are presented. Results: Both switching strategies were well tolerated. Rates of discontinuation for any reason were similar between the groups. Discontinuations due to adverse events were also similar, and the incidence of gastrointestinal adverse events was low. Apart from Alzheimer's Disease Cooperative Study–Activities of Daily Living Scale scores, at the end of the study, there was no statistically significant change from baseline in cognitive, behavioral, or global outcomes. Over half of the patients preferred rivastigmine transdermal patches to a tablet. Conclusions: This study suggests that the majority of patients receiving donepezil tablets can be safely switched to rivastigmine transdermal patches without significant deterioration in cognition, behavior, and global functioning. Trial Registration: clinicaltrials.gov Identifier: NCT00305903 PMID:21274364

  16. A method to visualize transdermal nickel permeation in mouse skin using a nickel allergy patch

    PubMed Central

    Sugiyama, Tomoko; Uo, Motohiro; Wada, Takahiro; Hongo, Toshio; Omagari, Daisuke; Komiyama, Kazuo; Oikawa, Masakazu; Kusama, Mikio; Mori, Yoshiyuki

    2015-01-01

    Metal patch test is often used in clinical settings when metal-induced contact dermatitis is suspected. However, the transdermal permeation behavior of metal ions from the patch test remains unclear. Current patch tests using high concentrations of metal salt solutions have some side effects, e.g. acute skin reactions to high concentrations of metal salt. To resolve these, estimating metal ion transdermal permeation is wished. In this study, synchrotron radiation X-ray fluorescence (SR-XRF) and micro-focused particle-induced X-ray emission (micro-PIXE) were used to visualize the time-dependent Ni permeation in mouse skin. The cross-sectional diffusion of Ni was visualized in a time-dependent manner. Our results indicate that maximum Ni permeation occurs after 24 h of patch treatment, and the permeated Ni content was high in the epidermis and spread into the dermis beyond the basal layer. This method may be useful to determine the appropriate solution concentration and duration of administration for the patch test. PMID:26484550

  17. Formulation and optimization of desogestrel transdermal contraceptive patch using crystallization studies.

    PubMed

    Sachdeva, Vishal; Bai, Yun; Kydonieus, Agis; Banga, Ajay K

    2013-01-30

    Levonorgestrel (LNG) is the most commonly used progestin in contraception. In this study, we report the use of an alternative progestin, desogestrel, for transdermal contraception. The drug was found to be significantly more permeable as compared to LNG (p<0.05). Crystallization studies were used to select the best adhesive among acrylate (Duro-Tak 87-4098 and Duro-Tak 87-202A) and polyisobutylene (PIB, Duro-Tak 87-608A) pressure sensitive adhesives by determining the drug's saturation solubility in them. The use of copovidone and mineral oil as formulation excipients was investigated to increase drug loading in the PIB adhesive. Physical characterization of the patches was performed using in vitro drug release, content analysis, patch weight and thickness variations and rolling ball tack and peel adhesion studies. Optimized patches were evaluated for in vitro transdermal delivery across hairless rat skin. The saturation solubility of desogestrel was found to be approximately 49.3% (w/w) and 55.6% (w/w) in Duro-Tak 87-4098 and Duro-Tak 87-202A acrylate adhesives, respectively. The saturation solubility of desogestrel was significantly lower (3-4%, w/w) in the PIB adhesive. Mineral oil (10%, w/w) and copovidone (30%, w/w) were found to be optimum for increasing drug loading and patch cosmetics. Results from the physical characterization studies suggest that a uniform and reproducible 7 day drug-in-adhesive patch could be developed. PMID:23262424

  18. A method to visualize transdermal nickel permeation in mouse skin using a nickel allergy patch.

    PubMed

    Sugiyama, Tomoko; Uo, Motohiro; Wada, Takahiro; Hongo, Toshio; Omagari, Daisuke; Komiyama, Kazuo; Oikawa, Masakazu; Kusama, Mikio; Mori, Yoshiyuki

    2015-01-01

    Metal patch test is often used in clinical settings when metal-induced contact dermatitis is suspected. However, the transdermal permeation behavior of metal ions from the patch test remains unclear. Current patch tests using high concentrations of metal salt solutions have some side effects, e.g. acute skin reactions to high concentrations of metal salt. To resolve these, estimating metal ion transdermal permeation is wished. In this study, synchrotron radiation X-ray fluorescence (SR-XRF) and micro-focused particle-induced X-ray emission (micro-PIXE) were used to visualize the time-dependent Ni permeation in mouse skin. The cross-sectional diffusion of Ni was visualized in a time-dependent manner. Our results indicate that maximum Ni permeation occurs after 24 h of patch treatment, and the permeated Ni content was high in the epidermis and spread into the dermis beyond the basal layer. This method may be useful to determine the appropriate solution concentration and duration of administration for the patch test. PMID:26484550

  19. Formulation and evaluation of anti-rheumatic dexibuprofen transdermal patches: a quality-by-design approach.

    PubMed

    Akhlaq, Muhammad; Arshad, Muhammad Sohail; Mudassir, Abdul Mughees; Hussain, Amjad; Kucuk, Israfil; Haj-Ahmad, Rita; Rasekh, Manoochehr; Ahmad, Zeeshan

    2016-08-01

    Dexibuprofen (DXIBN) transdermal patches were formulated using various concentrations of selected polymeric excipients (matrix material; ethyl cellulose and polyvinylpyrrolidone, plasticizer (di-N-butyl phthalate), and a conventional permeation enhancer (almond oil)). Initial patch formulations were evaluated for their physiochemical properties (thickness, moisture uptake, final moisture content, and DXIBN content). Also, impact of patch components on resulting tensile strength and in vitro permeation were used to predict an optimal patch formulation using a quality-by-design (QbD) approach, which was subsequently evaluated and further compared with a commercial oral tablet dosage form for in vitro and in vivo release (rabbit model). Initially formulated patches demonstrated uniform thickness (0.44 ± 0.02 cm), relatively low moisture uptake (7.87 ± 1.11 w/w %), and highly acceptable drug loading values (100.0 ± 0.026%). The tensile strength of patches increased significantly with matrix polymer concentration and to a lesser degree with increase in plasticizer and permeation enhancer content, although these affected the permeation of DXIBN. Predicted properties (tensile strength and DXIBN steady-state flux) for the QbD-optimized formulation were in close agreement to experimental results. The QbD optimal patch formulation behavior differed significantly from the commercial tablet formulation in vivo. Such model-based predictions (QbD approach) will reduce cost and time in formulation development sciences. PMID:26586147

  20. Development and in vitro evaluation of a transdermal hydrogel patch for ferulic acid.

    PubMed

    Bai, Jie; Lu, Yang; Li, Peng-yue; Liu, Cong-min; Wu, Hui-chao; Wen, Ran; Du, Shou-ying

    2014-03-01

    Current work aimed to develop and evaluate a transdermal delivery system of hydrogel patch for ferulic acid to treat skin damage induced by UV radiation. VISCOMATE(TM) NP700, dihydroxy aluminium aminoacetate, glycerine, tartaric acid were used in combination in different ratios to design the hydrogel patch. In vitro release rate was selected as an index to optimize the formulation. The formulated hydrogel patch was evaluated by several parameters like tacking strength, cohesive strength, peeling strength, residuals after peeling and drug content determination. The in vitro penetration was determined by Franz diffusion technology with hairless mouse skin as permeability media. Different kinetics models were employed to simulate the release and penetrate patterns of ferulic acid from patches in order to investigate the drug transport mechanism. The residual drugs in the patch and skin were determined after the penetration experiment. The optimized preparation was dihydroxy aluminium aminoacetate: NP700: glycerine: ferulic acid as a ratio of 0.02:0.4:1.5:1.25:0.25. The cumulative percentage of release was 60.4465±1.7679% for 24h, which results from a combination of diffusion effect and polymer erosion effect. For the barrier of stratum corneum, the cumulative penetrate rate was only 1.3156±0.3588% and the release mechanism turn out to be the effect of erosion of polymer surface. The residual drugs in the patch were 97.5949±1.4932%. The in vitro data revealed that it was easy for ferulic acid to release from the paste while difficult to permeate through the skin barrier, which resulted in most of drugs residued in the paste. Hence, further experiments will be necessary for finding the penetration enhancer in ferulic acid transdermal delivery. PMID:24577928

  1. Lidocaine Transdermal Patch: Pharmacokinetic Modeling and In Vitro-In Vivo Correlation (IVIVC).

    PubMed

    Kondamudi, Phani Krishna; Tirumalasetty, Phani Prasanth; Malayandi, Rajkumar; Mutalik, Srinivas; Pillai, Raviraj

    2016-06-01

    The present study aims to develop the correlation between in vitro and in vivo skin permeation of lidocaine in its transdermal patch. In order to minimize the run-to-run variability during in vitro skin permeation studies, release normalized cumulative percent (%Ct n) was calculated. A suitable polynomial mathematical model was used to establish a correlation between time and %Ct n. Percent in vivo absorbed was calculated by using numerical deconvolution (NDC) and non-compartmental analysis (NCA) methods. Pharmacokinetic (PK) parameters such as AUC last and C max were predicted with the established in vitro-in vivo correlation (IVIVC) models. The minimum prediction errors in NDC method for C max were found to be -30.9 and -25.4% for studies I (in vivo study in human volunteers with one batch of Lidoderm patch; internal validation) and II (in vivo study in human volunteers with another batch of Lidoderm patch; external validation), respectively, whereas minimum prediction errors in NCA method were relatively low (3.9 and 0.03% for studies I and II, respectively) compared to those in NDC method. The prediction errors for AUC last were found to be less than 2% for both methods and studies. The established method in this study could be a potential approach for predicting the bioavailability and/or bioequivalence for transdermal drug delivery systems. PMID:26283198

  2. Percutaneous penetration of felbinac after application of transdermal patches: relationship with pharmacological effects in rats.

    PubMed

    Shinkai, Norihiro; Korenaga, Kazuko; Takizawa, Hiromi; Mizu, Hideo; Yamauchi, Hitoshi

    2008-01-01

    We have evaluated the percutaneous penetration of felbinac following application of topical patches using a microdialysis technique, and have examined correlations with pharmacological effects. A linear microdialysis probe with a 20-mm dialysis fibre was inserted into the skin of anaesthetized rats. Probe perfusion was started at 2.0 microL min(-1) with physiological saline and after a 60-min baseline sampling of dialysate, 0.1 mL croton oil was applied to the skin surface at a concentration of 8%, v/v. A felbinac patch was then applied to the same point 60 min thereafter and dialysate was sampled at 60-min intervals up to 300 min after patch application, for determination of concentrations of felbinac and prostaglandin (PG) E2. Analgesic effects of felbinac patches in an iodoacetateinduced osteoarthritis model and an incisional pain model were evaluated using the weight bearing method. After application of patches, felbinac penetration into the skin was rapid, maximum concentrations in the dialysates with 0.07, 0.5 and 3.5% w/w felbinac patches being 0.046+/-0.02, 0.104+/-0.06 and 0.244+/-0.2 microg mL(-1), respectively. Dermal administration of croton oil caused an increment in PGE2 levels, which was significantly decreased by 0.5 and 3.5% felbinac patches 2-5 h after application. In pharmacological studies, 3.5% felbinac patches suppressed pain-associated behaviour induced by iodoacetate injection and plantar incision. These results suggested that the transdermal patch containing 3.5% felbinac may become a useful formulation. PMID:18088507

  3. Conductive polymer nanotube patch for fast and controlled in vivo transdermal drug delivery

    NASA Astrophysics Data System (ADS)

    Nguyen, Thao M.

    Transdermal drug delivery has created new applications for existing therapies and offered an alternative to the traditional oral route where drugs can prematurely metabolize in the liver causing adverse side effects. Opening the transdermal delivery route to large hydrophilic drugs is one of the greatest challenges due to the hydrophobicity of the skin. However, the ability to deliver hydrophilic drugs using a transdermal patch would provide a solution to problems of other delivery methods for hydrophilic drugs. The switching of conductive polymers (CP) between redox states cause simultaneous changes in the polymer charge, conductivity, and volume—properties that can all be exploited in the biomedical field of controlled drug delivery. Using the template synthesis method, poly(3,4-ethylenedioxythiophene (PEDOT) nanotubes were synthesized electrochemically and a transdermal drug delivery patch was successfully designed and developed. In vitro and in vivo uptake and release of hydrophilic drugs were investigated. The relationship between the strength of the applied potential and rate of drug release were also investigated. Results revealed that the strength of the applied potential is proportional to the rate of drug release; therefore one can control the rate of drug release by controlling the applied potential. The in vitro studies focused on the kinetics of the drug delivery system. It was determined that the drug released mainly followed zero-order kinetics. In addition, it was determined that applying a releasing potential to the transdermal drug delivery system lead to a higher release rate constant (up to 7 times greater) over an extended period of time (˜24h). In addition, over 24 hours, an average of 80% more model drug molecules were released with an applied potential than without. The in vivo study showed that the drug delivery system was capable of delivering model hydrophilic drugs molecules through the dermis layer of the skin within 30 minutes

  4. Pharmacokinetics of non-intravenous formulations of fentanyl.

    PubMed

    Lötsch, Jörn; Walter, Carmen; Parnham, Michael J; Oertel, Bruno G; Geisslinger, Gerd

    2013-01-01

    Fentanyl was structurally designed by Paul Janssen in the early 1960s as a potent opioid analgesic (100-fold more potent than morphine). It is a full agonist at μ-opioid receptors and possesses physicochemical properties, in particular a high lipophilicity (octanol:water partition coefficient >700), which allow it to cross quickly between plasma and central nervous target sites (transfer half-life of 4.7-6.6 min). It undergoes first-pass metabolism via cytochrome P450 3A (bioavailability ~30 % after rapid swallowing), which can be circumvented by non-intravenous formulations (bioavailability 50-90 % for oral transmucosal or intranasal formulations). Non-intravenous preparations deliver fentanyl orally-transmucosally, intranasally or transdermally. Passive transdermal patches release fentanyl at a constant zero-order rate for 2-3 days, making them suitable for chronic pain management, as are iontophoretic transdermal systems. Oral transmucosal and intranasal routes provide fast delivery (time to reach maximum fentanyl plasma concentrations 20 min [range 20-180 min] and 12 min [range 12-21 min], respectively) suitable for rapid onset of analgesia in acute pain conditions with time to onset of analgesia of 5 or 2 min, respectively. Intranasal formulations partly bypass the blood-brain barrier and deliver a fraction of the dose directly to relevant brain target sites, providing ultra-fast analgesia for breakthrough pain. Thanks to the development of non-intravenous pharmaceutical formulations, fentanyl has become one of the most successful opioid analgesics, and can be regarded as an example of a successful reformulation strategy of an existing drug based on pharmacokinetic research and pharmaceutical technology. This development broadened the indications for fentanyl beyond the initial restriction to intra- or perioperative clinical uses. The clinical utility of fentanyl could be expanded further by more comprehensive mathematical characterizations of its parametric

  5. Pharmacokinetic and biodistribution study of eserine and pralidoxime chloride in rabbits following a single application of a transdermal patch.

    PubMed

    Banerjee, Subham; Chattopadhyay, Pronobesh; Ghosh, Animesh; Bhatnagar, Aseem; Veer, Vijay

    2016-06-01

    In the present study, a simple reverse-phase high-performance liquid chromatography method with diode array detection has been developed and validated for the simultaneous determination and quantification of eserine and pralidoxime chloride in rabbit plasma and its application to pharmacokinetic study. The pharmacokinetic study was performed after transdermal application of single patch in rabbits. The plasma levels of both drugs following transdermal application of single patch were maintained for 72 h after removal of the patch. The maximal concentrations (C max) of both drugs were significantly reduced while the mean areas under the plasma concentration vs. time moment curve and mean residence times were evidently increased and extended, respectively. A sustained activity was observed over a period of 3 days. This sustained activity was due to the controlled release of drug into the systemic circulation following transdermal application. Linear correlation was also observed when fraction of drug permeated was correlated with the fraction of drug absorbed at the same time point. Gamma scintigraphy imaging on rabbit following transdermal patch application was performed to ascertain the localization of drugs in rabbit brain. PMID:25547639

  6. Design, development and permeation studies of nebivolol hydrochloride from novel matrix type transdermal patches

    PubMed Central

    Jatav, Vijay Singh; Saggu, Jitender Singh; Sharma, Ashish Kumar; Sharma, Anil; Jat, Rakesh Kumar

    2013-01-01

    Background: Nebivolol hydrochloride is a third generation β-blocker with highly selective β1-receptor antagonist with antihypertensive properties having plasma half life of 10 h and 12% oral bioavailability. The aim of the present investigation was to form matrix type transdermal patches containing Nebivolol hydrochloride to avoid its extensive hepatic first pass metabolism, lesser side effect and increase bioavailability of drug. Materials and Methods: Matrix type transdermal patches containing Nebivolol hydrochloride were prepared using EudragitRS100, HPMC K100M (2:8) polymers by solvent evaporation technique. Aluminum foil was used as a backing membrane. Polyethylene glycol (PEG) 400 was used as plasticizer and Dimethyl sulfoxide (DMSO) was used as a penetration enhancer. Drug polymer interactions determined by FTIR and standard calibration curve of Nebivolol hydrochloride were determined by using UV estimation. Result: The systems were evaluated physicochemical parameters and drug present in the patches was determined by scanning electron microscopy. All prepared formulations indicated good physical stability. In vitro drug permeation studies of formulations were performed by using Franz diffusion cells using abdomen skin of Wistar albino rat. Result showed best in vitro skin permeation through rat skin as compared to all other formulations prepared with hydrophilic polymer containing permeation enhancer. Conclusions: It was observed that the formulation containing HPMC: EudragitRS100 (8:2) showed ideal higuchi release kinetics. On the basis of in vitro drug release through skin permeation performance, Formulation F1 was found to be better than other formulations and it was selected as the optimized formulation. PMID:24223377

  7. The efficacy of low-dose transdermal fentanyl in opioid-naïve cancer patients with moderate-to-severe pain

    PubMed Central

    Kang, Jung Hun; Oh, Sung Yong; Song, Seo-Young; Lee, Hui-Young; Kim, Jung Han; Lee, Kyoung Eun; Lee, Hye Ran; Hwang, In Gyu; Park, Se Hoon; Kim, Won Seok; Park, Young Suk

    2015-01-01

    Background/Aims Little is known about the efficacy of low-dose transdermal fentanyl (TDF) patches in opioid-naïve patients with moderate-to-severe cancer pain. Methods This study had an open-label, prospective design, and was conducted between April 2007 and February 2009 in seven tertiary cancer hospitals; 98 patients were enrolled. TDF was started using a low-dose formulation (12.5 µg/hr), and the dose was adjusted according to the clinical situation of individual patients. Pain intensity, the TDF doses used, and adverse events (AEs) were monitored over 4 weeks. Data were analyzed using the intent-to-treat and per-protocol principles. Results Of the 98 patients enrolled, 64 (65%) completed the study. The median pain intensity decreased from 6.0 to 3.0 (p < 0.001) at the follow-up visit. The efficacy of low-dose TDF on pain relief was consistent across groups separated according to gender (p < 0.001), age (p < 0.001), metastasis (p < 0.001), previous treatment (p < 0.001), and baseline pain intensity (p < 0.001). The decrease in pain intensity was significantly greater in the severe group compared with the moderate group (mean ± SD, 5.10 ± 2.48 vs. 2.48 ± 1.56; p < 0.001). TDF dose (27.8 µg/hr vs. 24.8 µg/hr, p = 0.423) and the mean treatment time (7.5 days vs. 7.9 days, p = 0.740) required for pain control were not different between the two pain-intensity groups. Patients had AEs of only mild or moderate intensity; among these, nausea (38%) was the most common, followed by vomiting (22%) and somnolence (22%). Conclusions Low-dose TDF was an effective treatment for patients with cancer pain of moderate-to-severe intensity. Further randomized trials assessing the efficacy of TDF for severe pain and/or optimal starting doses are warranted. PMID:25589840

  8. Development of drug-in-adhesive patch formulations for transdermal delivery of fluoxetine: In vitro and in vivo evaluations.

    PubMed

    Jung, Eunjae; Lee, Eun Young; Choi, Hoo-Kyun; Ban, Sang-Jun; Choi, Seung-Hyuk; Kim, Jung Sun; Yoon, In-Soo; Kim, Dae-DuK

    2015-06-20

    The aim of this study was to develop drug-in adhesive (DIA) patch formulations for the transdermal delivery of fluoxetine (FX). The DIA patch formulations containing FX were prepared and optimized with various pressure sensitive adhesives, drug contents and enhancers. Among the various formulations, DuroTak 87-502B-based patch formulation containing 20% (w/w) FX with no enhancer was selected for in vivo pharmacokinetic study based on in vitro permeation studies using hairless mouse, rat and human cadaver skins. The Cmax of FX after the transdermal administration of the optimized patch formulation in rats was 52.38 ng/ml, and plasma concentration of FX was maintained for 36 h. Moreover, the predicted human Css (55.79 ng/ml) and Cmax (27.35 ng/ml) were in good agreement with the reported plasma levels (15-55 ng/ml) of oral FX in clinical applications. These results suggest that the optimized patch formulation could be further developed for clinical applications, providing the therapeutic plasma level of FX over an extended period. To the best of our knowledge, our results are the first reported in vitro and in vivo data on the preparation and optimization of FX-loaded DIA patch, showing its feasibility as an effective transdermal delivery system for FX. PMID:25863117

  9. Design and evaluation of matrix diffusion controlled transdermal patches of verapamil hydrochloride.

    PubMed

    Kusum Devi, V; Saisivam, S; Maria, G R; Deepti, P U

    2003-05-01

    Transdermal patches of verapamil hydrochloride were prepared using four different polymers (individual and combination): Eudragit RL100 (ERL100), Eudragit RS100 (ERS100), hydroxypropyl methylcellulose 15 cps (HPMC), and ethyl cellulose (EC), of varying degrees of hydrophilicity and hydrophobicity. The effect of the polymers on the technological properties, i.e., drug release, water vapor transmission rate (WVTR), and percentage moisture loss (ML), percentage moisture absorption (MA), folding endurance, and thickness, was investigated. Different formulations were prepared in accordance with the 2(3) factorial design, with ERL100 being the parent polymer. The patch containing ERL100 alone showed maximum WVTR, % MA, and % ML, which could be attributed to its hydrophilic nature. As expected, substitution with ERS100, HPMC, and EC decreased all the above values in accordance with their decreasing degree of hydrophilicity. In vitro release studies showed zero-order release of the drug from all the patches, and the mechanism of release was diffusion mediated. Moreover, the release of the drug was sustained and it extended over a period of 24 hr in all formulations. A12 emerged as the most satisfactory formulation insofar as its technological properties were concerned. Further, release and permeation of the drug from the most satisfactory formulation (A12) was evaluated through different biological barriers (shed snake skin, rabbit skin, and rat skin) to get an idea of the drug permeation through human skin. Shed snake's skin was found to be most permeable (82.56% drug release at 24 hr) and rat skin was least permeable (52.38%). Percutaneous absorption studies were carried out in rabbits. The pharmacokinetic parameters calculated from blood levels of the drug revealed a profile typical of a sustained release formulation, with the ability to maintain adequate plasma levels for 24 hr. [AUC: 3.09 mg/mL hr, Cmax: 203.95 microg/mL, Tmax: 8 hr]. It can therefore be concluded

  10. Transdermal fentanyl improves pain control and functionality in patients with osteoarthritis: an open-label Canadian trial.

    PubMed

    Choquette, Denis; McCarthy, Timothy G; Rodrigues, Jude F N; Kelly, Allan J; Camacho, Fernando; Horbay, G L A; Husein-Bhabha, Farah A

    2008-05-01

    Current treatment guidelines advocate opioids for arthritis when standard analgesics produce inadequate relief. Efficacy, adverse effects (AEs), dosing regimens, physician expertise and patient preference influence treatment selection. This study assessed transdermal fentanyl (TDF) as a treatment option for osteoarthritis (OA) patients. This prospective, Canadian open-label, 8-week trial assessed the efficacy and safety of TDF in patients with OA of hip or knee with moderate-to-severe target joint pain inadequately controlled using weak opioids. TDF was initiated at 25 mcg/h and titrated to optimal pain control. Rescue acetaminophen 500 mg was allowed (maximum 4 g/day). The main endpoint was improvement in pain control assessment rating (five rating categories); pain intensity (0-10 numerical scale), functionality (WOMAC-OA Index), health-related quality of life (SF-36 Health Survey) and global impression were also evaluated. Eighty-one patients (61% female, mean age 60 years) were enrolled; 62 were evaluable. All had failed on previous weak opioid therapy, primarily codeine or codeine combinations. At treatment end, 65% rated pain control as improved (Pain Control Assessment rating change >or=1 category; p<0.0001); mean change in pain intensity was a reduction of greater than 2 (p<0.0001); almost 50% were maintained on TDF 25 mcg/h with less than 1.3 g/day of rescue acetaminophen. At 1 month and end of treatment, changes in the SF-36 physical global scale and individual sub-scores for the pain index and role-physical scales were highly significant (p<0.0001). Improvement in functionality was noted at 1 month and at end of treatment with significant reductions in total WOMAC score, individual pain, stiffness and physical function sub-scores (p<0.0001). AEs causing discontinuation (n=32) included nausea, dizziness and vomiting. Most treatment-related AEs were mild to moderate in intensity. TDF improved pain control, functionality and health-related quality of life

  11. In vitro and in vivo evaluation of a hydrogel-based prototype transdermal patch system of alfuzosin hydrochloride.

    PubMed

    Nair, Anroop B; Vaka, Siva Ram Kiran; Gupta, Sumit; Repka, Michael A; Murthy, S Narasimha

    2012-01-01

    The first-line therapy for moderate to severe benign prostatic hyperplasia is the oral therapy by alfuzosin hydrochloride. Unfortunately, the oral therapy of alfuzosin is associated with several route-specific systemic side-effects. The current study was aimed to develop a prototype transdermal patch system for alfuzosin using a hydrogel polymer and optimize the drug delivery through the skin for systemic therapy. The prospective of different chemical enhancers (polyethylene glycol (PEG 400), isopropyl myristate, propylene glycol, menthol and L-methionine; 5% w/v) and iontophoresis (0.3 mA/cm(2)) in the alfuzosin delivery across the full thickness rat skin was assessed in vitro. In vivo iontophoretic studies were carried out using selected patch system (PEG 400) for a period of 6 h in Sprague-Dawley rats. Passive permeation studies indicated that the incorporation of chemical agents have moderate effect (~4- to 7-fold) on the alfuzosin skin permeability and reduced the lag time. Combined approach of iontophoresis with chemical enhancers significantly augmented the drug transport (~ 43- to 72-fold). In vivo pharmacokinetic parameters revealed that the iontophoresis (transdermal patch with PEG 400) significantly enhanced the C(max) (~ 3-fold) and AUC(0-α) (~ 4-fold), when compared to control. The current study concludes that the application of iontophoresis (0.3 mA/cm(2)) using the newly developed agaorse-based prototype patch with PEG 400 could be utilized for the successful delivery of alfuzosin by transdermal route. PMID:20958130

  12. Bioavailability, bioequivalence, and in vitro-in vivo correlation of oxybutynin transdermal patch in rabbits.

    PubMed

    Khire, Achyut; Vavia, Pradeep

    2014-04-01

    The first objective of the proposed research work includes comparative bioavailability and bioequivalence evaluation of oxybutynin transdermal patch with respect to different permeation enhancers. The second objective was to evaluate different in vitro methods along with synthetic membranes toward development of an in vitro-in vivo correlation. Oleic acid (fatty acid), Soluphor P (2-pyrrolidone, cosolvent), menthol (volatile oil), and dipropylene glycol (plasticizer) were selected as representatives from different classes of permeation enhancers. A random, crossover, single-dose pharmacokinetic study was carried out on male New Zealand white rabbits to determine bioavailability and bioequivalence. The obtained pharmacokinetic data were correlated with in vitro drug release using convolution-deconvolution approach. All developed formulations were found to be bioequivalent with respect to the marketed patch (Oxytrol®) on the basis of level of C max, AUC0-96, and AUCtotal (0.8-1.25). A biphasic linear correlation was obtained pertaining to differential diffusion behavior of the drug in vivo during the experimental timeframe. Because of close resemblance to skin, Cuprophan® membrane was found to be more suitable for developing an IVIVC than Millipore® membrane. PMID:25786724

  13. Design and characterization of diclofenac diethylamine transdermal patch using silicone and acrylic adhesives combination

    PubMed Central

    2013-01-01

    Background and purpose of the study The objective of the study was to develop and characterize Diclofenac Diethylamine (DDEA) transdermal patch using Silicone and acrylic adhesives combination. Methods Modified solvent evaporation method was employed for casting of film over Fluoropolymer coated polyester release liner. Initial studies included solubilization of drug in the polymers using solubilizers. The formulations with combination of adhesives were attempted to combine the desirable features of both the adhesives. The effect of the permeation enhancers on the drug permeation were studied using pig ear skin. All the optimized patches were subjected to adhesion, dissolution and stability studies. A 7-day skin irritancy test on albino rabbits and an in vivo anti-inflammatory study on wistar rats by carrageenan induced paw edema method were also performed. Results The results indicated the high percent drug permeation (% CDP-23.582) and low solubility nature (1%) of Silicone adhesive and high solubility (20%) and low% CDP (10.72%) of acrylic adhesive. The combination of adhesives showed desirable characteristics for DDEA permeation with adequate % CDP and sufficient solubility. Release profiles were found to be dependent on proportion of polymer and type of permeation enhancer. The anti-inflammatory study revealed the sustaining effect and high percentage inhibition of edema of C4/OLA (99.68%). The acute skin irritancy studies advocated the non-irritant nature of the adhesives used. Conclusion It was concluded that an ideal of combination of adhesives would serve as the best choice, for fabrication of DDEA patches, for sustained effect of DDEA with better enhancement in permeation characteristics and robustness. PMID:23351568

  14. Potential biomarkers of smoked fentanyl utilizing pyrolysis gas chromatography-mass spectrometry.

    PubMed

    Nishikawa, Rona K; Bell, Suzanne C; Kraner, James C; Callery, Patrick S

    2009-10-01

    Fentanyl is a potent opioid analgesic that is increasingly becoming a choice drug of abuse. Fentanyl transdermal patches (FTPs) are easily obtained and consumed by smoking the reservoir gel and/or the whole patch. This allows for an increased bioavailability when inhaled. A method using analytical pyrolysis was developed to identify possible biomarkers associated with smoked fentanyl and FTPs. Pyrolysis was carried out under anaerobic and aerobic conditions using helium and air coupled to a gas chromatograph-mass spectrometer. The presence of a trap enhanced recovery and afforded a positive identification of pyrolytic products. Anaerobic and aerobic pyrolysis of fentanyl and FTPs consistently yielded propionanilide as the major pyrolytic product along with pyridine and previously reported metabolites (norfentanyl and despropionyl fentanyl). Analysis of fentanyl resulted in chlorine-containing compounds, presumably formed from the HCl salt of fentanyl. Analysis of FTPs showed significant polymeric and hydrocarbon compounds and products likely derived from the gel matrix. Fentanyl in the FTPs was in the citrate salt form; therefore, the chlorine-containing pyrolytic products obtained with the neat drug were not observed. Based on this application, it may be possible to identify what salt form of the drug was smoked based on pyrolytic products and to target distinguishing metabolic products for future research. PMID:19874647

  15. Consideration of sex in clinical trials of transdermal nicotine patch: A systematic review

    PubMed Central

    Weinberger, Andrea H.; Smith, Philip H.; Kaufman, Mira; McKee, Sherry A.

    2014-01-01

    Transdermal nicotine patch (TNP) is one of the most commonly used smoking cessation treatments; however, the efficacy of TNP by sex is not yet clear. The purpose of the current review was to synthesize how sex has been considered in published clinical trials of TNP for smoking cessation. The specific aims of the study were to examine the inclusion of sex in analyses of cessation outcomes, TNP-related variables (compliance, side effects), and quit-related variables (withdrawal, cravings); to review the consideration of sex-related variables (menstrual cycle phase, pregnancy); and to identify needs for future research. Potential articles published through December 31, 2013 were identified through a MEDLINE search of the terms “clinical trial,” “nicotine patch,” and “smoking cessation.” Forty-two studies used all three terms and met the inclusion criteria. Half of the studies reported that they considered sex in smoking cessation outcomes with 14 studies finding no difference by sex and 7 studies finding better outcomes for men versus women. Only 5 studies reported data on outcomes by sex in their publications. No studies reported analysis of TNP compliance or withdrawal by sex. In the one study that examined side effects by sex, more women than men reported discontinuing TNP due to skin irritation. No study examined the association of cessation outcomes with menstrual cycle phase. There is a need to include sex in research on TNP, as well as other pharmacological and behavioral smoking treatments, to clarify the picture of treatment efficacy for women compared to men. PMID:25133506

  16. Ketotifen Fumarate and Salbutamol Sulphate Combined Transdermal Patch Formulations: In vitro release and Ex vivo Permeation Studies.

    PubMed

    Yousuf, M; Ahmad, M; Usman, M; Ali, I

    2013-09-01

    The present work was performed to develop and evaluate transdermal patches of combined antiasthmatic drugs (salbutamol sulphate and ketotifen fumarate). Polyvinyl alcohol membrane was used as backing membrane and eudragit RL-100 was used as matrix material to suspend the drugs in the continuous thickness of the patch. Methanol was solvent and propylene glycol was used as plasticizer. Tween 20, isopropyl myristate, eucalyptus oil, castor oil and span-20 were used as permeability enhancers. Thickness, weight variation and drug uniformity were investigated. The patch formulations were also subjected to drug release in dissolution media and permeation through rabbit skin. Effects of different enhancers were evaluated on release and permeation of drugs. F3 formulations having isopropyl myristate as permeation enhancer, showed maximum amounts of drugs release (88.11% of salbutamol sulphate and 88.33% of ketotifen fumarate) at the end of 24 h dissolution study. F3 also showed maximum permeation of both drugs (4.235 mg salbutamol sulphate and 1.057 mg ketotifen fumarate) after 24 h permeation study through rabbit skin mounted in Franz cell. The patches having no enhancer in the formulation also showed some drug release and permeation due to the presence of plasticizer. The results of the study suggested that new controlled release transdermal formulations of combined antiasthmatic drugs can be suitably developed as an alternate to conventional dosage forms. PMID:24403658

  17. Ketotifen Fumarate and Salbutamol Sulphate Combined Transdermal Patch Formulations: In vitro release and Ex vivo Permeation Studies

    PubMed Central

    Yousuf, M.; Ahmad, M.; Usman, M.; Ali, I.

    2013-01-01

    The present work was performed to develop and evaluate transdermal patches of combined antiasthmatic drugs (salbutamol sulphate and ketotifen fumarate). Polyvinyl alcohol membrane was used as backing membrane and eudragit RL-100 was used as matrix material to suspend the drugs in the continuous thickness of the patch. Methanol was solvent and propylene glycol was used as plasticizer. Tween 20, isopropyl myristate, eucalyptus oil, castor oil and span-20 were used as permeability enhancers. Thickness, weight variation and drug uniformity were investigated. The patch formulations were also subjected to drug release in dissolution media and permeation through rabbit skin. Effects of different enhancers were evaluated on release and permeation of drugs. F3 formulations having isopropyl myristate as permeation enhancer, showed maximum amounts of drugs release (88.11% of salbutamol sulphate and 88.33% of ketotifen fumarate) at the end of 24 h dissolution study. F3 also showed maximum permeation of both drugs (4.235 mg salbutamol sulphate and 1.057 mg ketotifen fumarate) after 24 h permeation study through rabbit skin mounted in Franz cell. The patches having no enhancer in the formulation also showed some drug release and permeation due to the presence of plasticizer. The results of the study suggested that new controlled release transdermal formulations of combined antiasthmatic drugs can be suitably developed as an alternate to conventional dosage forms. PMID:24403658

  18. Role of intranasal fentanyl in breakthrough pain management in cancer patients

    PubMed Central

    Leppert, Wojciech

    2010-01-01

    Fentanyl is a strong opioid analgesic, which is commonly used in the form of a transdermal patch for the treatment of chronic cancer pain. An intranasal route of fentanyl administration is a novel treatment for breakthrough cancer pain (BTCP). The prevalence, assessment, and management of BTCP is outlined in this paper, and basic pharmacodynamic and pharmacokinetic properties, dosing guidelines, and clinical experience with the use of intranasal fentanyl in this indication are discussed. Intranasal fentanyl is an attractive and convenient mode of BTCP treatment in opioid-tolerant patients due to its quick onset and short duration of action, noninvasive administration route, high bioavailability, and avoidance of a hepatic first-pass effect. Until now, few clinical trials have been conducted with intranasal fentanyl, but all have confirmed its usefulness and acceptability in BTCP treatment. Intranasal fentanyl may be used in opioid-tolerant patients without nasal pathologies. The dose should be titrated in each patient regardless of the regular opioid dose administered. Future studies should compare intranasal fentanyl with other fentanyl formulations used for BTCP management, and with analgesia, adverse effects, and quality of life taken into consideration. PMID:21188114

  19. Effective use of transdermal drug delivery in children.

    PubMed

    Delgado-Charro, M Begoña; Guy, Richard H

    2014-06-01

    Transdermal administration offers a non-invasive and convenient method for paediatric drug delivery. The competent skin barrier function in term infants and older children limits both water loss and the percutaneous entry of chemicals including drugs; but the smaller doses required by children eases the attainment of therapeutic concentrations. Transdermal patches used in paediatrics include fentanyl, buprenorphine, clonidine, scopolamine, methylphenidate, oestrogens, nicotine and tulobuterol. Some patches have paediatric labelling supported by clinical trials whereas others are used unlicensed. Innovative drug delivery methods, such as microneedles and sonophoresis are being tested for their safety and efficacy; needleless injectors are primarily used to administer growth hormone; and two iontophoretic devices were approved for paediatrics. In contrast, the immature and rapidly evolving skin barrier function in premature neonates represents a significant formulation challenge. Unfortunately, this population group suffers from an absence of approved transdermal formulations, a shortcoming exacerbated by the significant risk of excessive drug exposure via the incompletely formed skin barrier. PMID:24333231

  20. Buprenorphine 5, 10 and 20 μg/h transdermal patch: a review of its use in the management of chronic non-malignant pain.

    PubMed

    Plosker, Greg L

    2011-12-24

    This article reviews the pharmacology, therapeutic efficacy and tolerability profile of the 7-day lower-dose (5, 10 and 20 μg/h) buprenorphine transdermal patch (BuTrans®, Norspan®) in the management of chronic non-malignant pain, with a focus on European labelling for the drug. Buprenorphine is a semi-synthetic opioid analgesic that acts primarily as a partial agonist at the mu opioid receptor. The transdermal formulation provides continuous delivery of buprenorphine, resulting in relatively consistent plasma drug concentrations throughout the 7-day dosing interval. The analgesic efficacy of transdermal buprenorphine in patients with osteoarthritis of the hip and/or knee has been demonstrated in several randomized controlled trials, which have shown the formulation to be equivalent to sublingual buprenorphine, noninferior to prolonged-release tramadol tablets, noninferior to codeine plus paracetamol (acetaminophen) combination tablets (when transdermal buprenorphine was used together with regularly scheduled oral paracetamol) and generally superior to a matching transdermal placebo patch. Transdermal buprenorphine was significantly more effective than placebo in reducing chronic low back pain of at least moderate severity in two randomized, double-blind, crossover trials. Other clinical trials, including a randomized, double-blind, maintenance-of-analgesia study, have also demonstrated the analgesic efficacy of transdermal buprenorphine in patients with chronic non-malignant pain of various causes. In general, serious adverse events with transdermal buprenorphine are similar to those for other opioid analgesics. Transdermal buprenorphine has a ceiling effect for respiratory depression, and the main risk is when it is combined with other CNS depressants. The most frequently reported adverse events with transdermal buprenorphine are headache, dizziness, somnolence, constipation, dry mouth, nausea, vomiting, pruritus, erythema, application site pruritus and

  1. [Transdermal rivastigmine patch in outpatient services in Austria: a naturalistic study in 103 patients with Alzheimer dementia].

    PubMed

    Schmidt, Reinhold; Alf, Claude; Bancher, Christian; Benke, Thomas; Berek, Klaus; Dal-Bianco, Peter; Führwürth, Gerhard; Imarhiagbe, Douglas; Jagsch, Christian; Lechner, Anita; Rainer, Michael; Reisecker, Franz; Rotaru, Juliana; Uranüs, Margarete; Walter, Andreas; Winkler, Andreas; Wuschitz, Albert

    2009-01-01

    We performed a 6-month open-label study on the use of the transdermal rivastigmine patch in clinical routine in 103 patients with Alzheimer's disease from 25 outpatient services in Austria. After baseline, safety and tolerability of the 10 cm2--rivastigmine patch was assessed at week 4, 12 and 24 in all patients. A Mini Mental State Examination was done at baseline and at week 12 and 24. Skin adherence of the patch was very good or good in 85% of study participants. Only 2.9% of patients had gastrointestinal adverse events. Local skin reactions occurred in 23% of individuals. Skin alteration were mostly mild in severity. In only 6.8% of subjects did they result in termination of treatment. At the earliest skin reactions were observed after 3 months of treatment. Cognitive functioning of patients improved comparable to the controlled trial which led to approval of the rivastigmine patch. In daily routine the safety profile of the rivastigmine patch is favourable, as is the response to treatment. Local, mostly mild skin reactions affect approximately every fifth patient, and they occur relatively late in the course of therapy. Patients and their caregivers should receive detailed information about skin reactions to omit unnecessary drop outs to treatment. PMID:19272293

  2. Modified TEWL in vitro measurements on transdermal patches with different additives with regard to water vapour permeability kinetics.

    PubMed

    Fokuhl, Joana; Müller-Goymann, Christel C

    2013-02-28

    Water vapour permeability (WVP) and water absorption capacity (WAC) influence physicochemical properties and wearability of transdermal patches considerably. For determination of WVP, a modified transepidermal water loss (TEWL) measurement was developed. These measurements continuously measure WVP of transdermal patches in vitro along with time required to reach steady state, and its magnitude according to the type of polymer used. Additionally, WAC of the patches was examined and related to WVP. According to literature in the field of WVP determination, usually selected points are taken from the evaporation time curve and averaged over a given time span without knowing whether steady state has already been reached or not. The latter causes errors upon averaging. The advantage of the in vitro TEWL measurement presented includes reproducibly adjustable conditions for every time span desired, thus providing information on the kinetics of the experiment and avoiding biased results from averaging. Knowing the shape of the evaporation time curve and thus the kinetics of the experiment allows for focusing on the relevant part of the measurement, i.e. the determination of the steady state level and the time to reach it. Four different polymers (P1-P4) based on sugar-modified polyacrylates were investigated with regard to WVP and WAC of the matrices prepared thereof along with the influence of drug loading and the incorporation of a variety of additives commonly used for transdermal patches. A clear correlation between WVP and the hydrophilicity in terms of the number of free hydroxyl groups of the polymer was elaborated. Additives of higher hydrophilicity compared to that of the polymer itself led to higher WVPs and vice versa. The combination of the model drug lidocaine in its free base form together with the additive succinic acid (Suc) resulted in ionization of the drug and thus in substantially increased WVPs. Addition of α-tocopherol acetate (Toc) into P3 and P4 and

  3. The safety and effectiveness of a long-acting transdermal fentanyl solution compared with oxymorphone for the control of postoperative pain in dogs: a randomized, multicentered clinical study

    PubMed Central

    Martinez, S A; Wilson, M G; Linton, D D; Newbound, G C; Freise, K J; Lin, T-L; Clark, T P

    2014-01-01

    A prospective, double-blinded, positive-controlled, multicenter, noninferiority study was conducted to evaluate the safety and effectiveness of transdermal fentanyl solution (TFS) compared with oxymorphone for the control of postoperative pain in dogs. Five hundred and two (502) client-owned dogs were assigned to a single dose of TFS (2.7 mg/kg) applied 2–4 h prior to surgery or oxymorphone hydrochloride (0.22 mg/kg) administered subcutaneously 2–4 h prior to surgery and q6h through 90 h. Pain was evaluated over 4 days by blinded observers using a modified Glasgow composite pain scale, and the a priori criteria for treatment failure was a pain score ≥8 or adverse event necessitating withdrawal. Four TFS- and eight oxymorphone-treated dogs were withdrawn due to lack of pain control. Eighteen oxymorphone-treated, but no TFS-treated dogs were withdrawn due to severe adverse events. The one-sided upper 95% confidence interval of the difference between TFS and oxymorphone treatment failure rates was −5.3%. Adverse events associated with oxymorphone were greater in number and severity compared with TFS. It was concluded that a single administration of TFS was safe and noninferior to repeated injections of oxymorphone for the control of postoperative pain over 4 days at the dose rates of both formulations used in this study. PMID:24344787

  4. Innovative delivery systems for migraine: the clinical utility of a transdermal patch for the acute treatment of migraine.

    PubMed

    Rapoport, Alan M; Freitag, Fred; Pearlman, Starr H

    2010-11-01

    . These studies also suggest that, by avoiding patient exposure to a rapid rise in and high plasma concentrations of sumatriptan as seen with injectable sumatriptan, transdermal delivery using iontophoresis may significantly reduce typical triptan-related adverse events. A large, randomized, double-blind, placebo-controlled, multicentre clinical trial showed statistically significant efficacy, good tolerability and virtually no triptan-related adverse events. Iontophoretic delivery of sumatriptan, with a novel transdermal patch device, offers patients a migraine-specific medication that is non-invasive and non-oral. Clinically, transdermal delivery provides rapid and effective relief of migraine while bypassing the gastrointestinal tract, with minimal classic triptan-related adverse effects. This unique approach facilitates the rapid absorption of this migraine-specific triptan, which should improve the chances of consistently achieving a therapeutic plasma concentration of sumatriptan, resulting in effective migraine relief. PMID:20932065

  5. Design and Evaluation of a Novel Felbinac Transdermal Patch: Combining Ion-Pair and Chemical Enhancer Strategy.

    PubMed

    Liu, Nannan; Song, Wenting; Song, Tian; Fang, Liang

    2016-04-01

    The aim of this study was to design a novel felbinac (FEL) patch with significantly higher (P < 0.05) skin permeation amount than the commercial product SELTOUCH® using ion-pair and chemical enhancer strategy, overcoming the disadvantage of the large application area of SELTOUCH®. Six complexes of FEL with organic amines diethylamine (DEA), triethylamine (TEA), N-(2'-hydroxy-ethanol)-piperdine (HEPP), monoethanolamine (MEtA), diethanolamine (DEtA), and triethanolamine (TEtA) were prepared by ion-pair interaction, and their formation were confirmed by differential scanning calorimetry (DSC), powder X-ray diffraction (pXRD), infared spectroscopy (IR), and proton nuclear magnetic resonance spectroscopy ((1)H-NMR). Subsequently, the effect of ion-pair complexes and chemical enhancers were investigated through in vitro and in vivo experiments using rabbit abdominal skin. Results showed that FEL-TEA was the most potential candidate both in isopropyl palmitate (IPP) solution and transdermal patches. Combining use of 10% N-dodecylazepan-2-one (Azone), the optimized FEL-TEA patch achieved a flux of 18.29 ± 2.59 μg/cm(2)/h, which was twice the amount of the product SELTOUCH® (J = 9.18 ± 1.26 μg/cm(2)/h). Similarly, the area under the concentration curve from time 0 to time t (AUC0-t ) in FEL-TEA patch group (15.94 ± 3.58 h.μg/mL) was also twice as that in SELTOUCH® group (7.31 ± 1.16 h.μg/mL). Furthermore, the in vitro skin permeation results of FEL-TEA patch was found to have a good correlation with the in vivo absorption results in rabbit. These findings indicated that a combination of ion-pair and chemical enhancer strategy could be useful in developing a novel transdermal patch of FEL. PMID:26070544

  6. Adhesion testing of polyurethane matrix patches for transdermal delivery of testosterone.

    PubMed

    Dittgen, M; Gansen, P

    2012-06-01

    The 180 degrees peel test was applied to measure adhesion of three experimental polyurethane (PU) matrix patches and one commercial patch, Testopatch, on human volunteers skin. Comparing the results with those measurements on stainless steel or leather, a significant correlation between the leather data and the skin measurements was found. In contrary to results from stainless steel tests, all of the PU patches achieved better adhesion on skin than the commercial patch. PMID:22822549

  7. A novel male contraceptive pill-patch combination: oral desogestrel and transdermal testosterone in the suppression of spermatogenesis in normal men.

    PubMed

    Hair, W M; Kitteridge, K; O'Connor, D B; Wu, F C

    2001-11-01

    This study investigated the effect of transdermal T and oral desogestrel on the reproductive axis of healthy men. Twenty-three men were randomized to 1 of 3 treatment groups and received a daily transdermal T patch plus oral desogestrel at a dose of 75, 150, or 300 microg/d for 24 wk. Baseline blood and semen samples were obtained and then every 4 wk thereafter for 32 wk. The outcome measures were sperm density and plasma levels of FSH, LH, total and free T. The results show a dose-dependent suppression of spermatogenesis and gonadotropins. Seven of the 17 subjects became azoospermic. Desogestrel (300 microg daily) in combination with 5 mg daily transdermal T was the most effective (57% azoospermic), whereas a dose of 75 microg was ineffective (0% azoospermic). Total and free plasma T were reduced by approximately 30%. High density lipoprotein cholesterol was significantly reduced. No serious side-effects were encountered. We conclude that daily self-administered desogestrel with transdermal T is capable of suppressing the male reproductive axis, although the efficacy was less marked and less consistent than injectable regimens. The lower efficacy is likely to be due to failure of the transdermal T system to maintain circulating T levels consistently in the required range. PMID:11701677

  8. Transdermal delivery of alprazolam from a monolithic patch: formulation based on in vitro characterization.

    PubMed

    Soler, L I; Boix, A; Lauroba, J; Colom, H; Domenech, J

    2012-10-01

    Alprazolam, a benzodiazepine widely used for the treatment of psychiatric disorders, has been aimed to be formulated in a transdermal delivery system (TDS) prototype. A series of TDS prototypes dosed in all cases at 0.35 mg·cm(-2) of alprazolam were prepared as a monolithic drug in adhesive matrix using acrylic pressure-sensitive adhesives (PSA) of acrylate vinyl acetate (Duro-tack(®)). The effects of several permeation enhancers as azone, transcutol, propylene glycol, dodecyl alcohol, decyl alcohol, diethanolamine, N-methyl pyrrolidone and lauric acid were studied. Prototypes have been characterized based on adhesion parameters (peel adhesion and shear adhesion), in vitro human skin permeation and in vitro drug release according to European Pharmacopoeia for the selected prototype. Best results show that a combination of permeation enhancers from different chemical groups is able to provide almost a 33 fold increase in the transdermal alprazolam flux of an aqueous saturated dispersion (from 0.054 ± 0.019 to 1.76 ± 0.21 μg h.cm(-2)). Based on these in vitro flux data, a predictive simulation of the achievable plasmatic levels was performed assuming a constant systemic infusion of drug. In summary, it is possible to obtain a prototype of a TDS of alprazolam with adequate adhesive properties (peel adhesion and shear adhesion) and able to predict sustained therapeutic plasmatic levels. PMID:22204649

  9. Formulation optimization of galantamine hydrobromide loaded gel drug reservoirs in transdermal patch for Alzheimer’s disease

    PubMed Central

    Woo, Fong Yen; Basri, Mahiran; Fard Masoumi, Hamid Reza; Ahmad, Mansor B; Ismail, Maznah

    2015-01-01

    Galantamine hydrobromide (GH) is an effective drug for Alzheimer’s disease. It is currently delivered via the oral route, and this might cause nausea, vomiting, and gastrointestinal disturbance. In the present work, GH was formulated in a gel-type drug reservoir and then optimized by using response surface methodology (RSM) based on central composite design. This optimization study involved three independent variables (carbopol amount, triethanolamine amount, and GH amount) and two dependent variables (cumulative drug release amount at 8 hours and the permeation flux of drug). Two models using expert design software were fitted into a quadratic polynomial model. The optimized gel was formulated with 0.89% w/w carbopol, 1.16% w/w triethanolamine, and 4.19% w/w GH. Optimization analysis revealed that the proposed formulation has the predicted cumulative drug release amount at 8 hours of 17.80 mg·cm−2 and the predicted permeation flux of 2.27 mg·cm−2/h. These predicted values have good agreement to actual cumulative drug release amount at 8 hours (16.93±0.08 mg·cm−2) and actual permeation flux (2.32±0.02 mg·cm−2/h). This optimized reservoir formulation was then fabricated in the transdermal patch system. This patch system has moderate pH, high drug content, and controlled drug-release pattern. Thus, this patch system has the potential to be used as the drug carrier for the treatment of Alzheimer’s disease. PMID:26089664

  10. New insights in oxybutynin chemical stability: Identification in transdermal patches of a new impurity arising from oxybutynin N-oxide rearrangement.

    PubMed

    Canavesi, Rossana; Aprile, Silvio; Giovenzana, Giovanni B; Di Sotto, Antonella; Di Giacomo, Silvia; Del Grosso, Erika; Grosa, Giorgio

    2016-03-10

    Oxybutynin hydrochloride (Oxy), the first choice drug used for the management of urinary incontinence, is available in different types of formulations. However, due to its better lipophylicity and permeability, Oxyfree base was used in the new topical formulations such as transdermal patch and gel. The presence of an unprecedented impurity (Oxy-EK) in transdermal patches led to reinvestigate the chemical stability of Oxyfree base in oxidative conditions assigning, to Oxy-EK, the structure of (3E)-4-(N,N-diethylamino)-2-oxo-3-buten-1-yl 1-cyclohexyl-1-phenylglycolate. Oxy-EK arises from the prototropic rearrangement of oxybutynin N-oxides leading to the formation of an enamino ketone function which shows a long-wavelength UV-absorption. The total synthesis of Oxy-EK was performed, allowing to propose it as the indicator of stability for oxidative degradation of Oxy free base in transdermal formulations. The presence in the structure of Oxy-EK of an α,β-unsaturated carbonyl function, a potential Michael acceptor, suggested the need of evaluating its possible mutagenic power. Accordingly, the Ames test was performed: at nontoxic concentrations, Oxy-EK did not increase the number of revertant colonies in all strains tested both in the absence and presence of the exogenous metabolic activator S9. PMID:26796144

  11. The fentanyl story.

    PubMed

    Stanley, Theodore H

    2014-12-01

    Fentanyl, introduced more than 50 years ago, has become the most often used opioid for intraoperative analgesia. Since the early 1990s the fentanyl patch has been available for management of chronic pain of all forms of cancer as well as the persistent, intense pain from many noncancerous maladies. More than a half dozen rapid-onset transmucosal fentanyl preparations have been developed, approved, launched, and popularized for "breakthrough" pain syndromes in the past 20 years. The purpose of this article is to describe why this opioid has become so important in the treatment of pain in modern clinical practice. The data indicate that fentanyl's popularity has occurred because it has minimal cardiovascular effects, does not result in increases in plasma histamine, is relatively short in onset of action and duration of effect, is easy and inexpensive to synthesize and prepare for the marketplace, and is now familiar to clinicians working in pain and perioperative medicine throughout the world. PMID:25441689

  12. Estradiol Transdermal Patch

    MedlinePlus

    ... can benefit most from the medication. Women whose only bothersome symptoms are vaginal dryness, itching, or burning ... is applied topically to the vagina. Women who only need a medication to prevent osteoporosis may benefit ...

  13. Testosterone Transdermal Patch

    MedlinePlus

    ... not produce enough natural testosterone). Testosterone is used only for men with low testosterone levels caused by ... are a controlled substance. Prescriptions may be refilled only a limited number of times; ask your pharmacist ...

  14. Clonidine Transdermal Patch

    MedlinePlus

    ... agonist hypotensive agents. It works by decreasing your heart rate and relaxing the blood vessels so that blood ... Your doctor may ask you to check your pulse (heart rate) daily and will tell you how ...

  15. Buprenorphine Transdermal Patch

    MedlinePlus

    ... Posted 03/22/2016]AUDIENCE: Family Practice, Psychiatry, Pain Management, Nursing, EndocrinologyISSUE: FDA is warning about several safety issues with the entire class of opioid pain medicines. See the http://www.fda.gov/Drugs/ ...

  16. Oxybutynin Transdermal Patch

    MedlinePlus

    ... can use baby oil or a medical adhesive removal pad to remove residue that will not come ... room temperature and away from excess heat and moisture (not in the bathroom).Unneeded medications should be ...

  17. Clonidine Transdermal Patch

    MedlinePlus

    ... agonist hypotensive agents. It works by decreasing your heart rate and relaxing the blood vessels so that blood ... doctor may ask you to check your pulse (heart rate) daily and will tell you how rapid it ...

  18. Estradiol Transdermal Patch

    MedlinePlus

    ... estrogen product that is applied topically to the vagina. Women who only need a medication to prevent ... swelling, redness, burning, irritation or itching of the vagina vaginal discharge painful menstrual periods anxiety depression changes ...

  19. Buprenorphine Transdermal Patch

    MedlinePlus

    ... other condition that caused high pressure inside your skull; biliary tract disease; slowed heartbeat; low blood pressure; ... overdose may include the following: small, pinpoint pupils (black circles in the center of the eye) extreme ...

  20. Rotigotine Transdermal Patch

    MedlinePlus

    ... pads, electric blankets and heated waterbeds; or direct sunlight. Do not take a hot bath or use ... rash, do not expose this area to direct sunlight until the skin heals. Exposure of this area ...

  1. Nitroglycerin Transdermal Patch

    MedlinePlus

    ... Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for ...

  2. Testosterone Transdermal Patch

    MedlinePlus

    ... Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for ...

  3. Nicotine Transdermal Patch

    MedlinePlus

    ... Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for ...

  4. Rivastigmine Transdermal Patch

    MedlinePlus

    ... disease (a brain disease that slowly destroys the memory and the ability to think, learn, communicate and ... movement, muscle weakness, shuffling walk, and loss of memory). Rivastigmine is in a class of medications called ...

  5. Oxybutynin Transdermal Patch

    MedlinePlus

    ... can use baby oil or a medical adhesive removal pad to remove residue that will not come ... as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this ...

  6. Transdermal delivery of testosterone.

    PubMed

    Hadgraft, Jonathan; Lane, Majella E

    2015-05-01

    Male hypogonadism has been treated with exogenous testosterone since the 1930s. The early transdermal patches of testosterone became available in the 1980s with gel and solution preparations following subsequent decades. This review focusses on the skin permeation characteristics of testosterone, pharmacokinetics following application of transdermal formulations and formulations currently available. At present, gels dominate the market for transdermal testosterone replacement therapy, presumably because of their greater patient acceptability and non-occlusive nature compared with patches. However, specific incidences of secondary transfer of gels to children with consequent unwanted effects such as precocious puberty have been reported. A regulatory review of all testosterone replacement therapies is currently underway which may have implications for future prescribing practices of transdermal testosterone products. PMID:25709060

  7. Transdermal Delivery of Insulin by Amidated Pectin Hydrogel Matrix Patch in Streptozotocin-Induced Diabetic Rats: Effects on Some Selected Metabolic Parameters

    PubMed Central

    Hadebe, Silindile I.; Ngubane, Phikelelani S.; Serumula, Metse R.; Musabayane, Cephas T.

    2014-01-01

    Purpose Studies in our laboratory are concerned with developing optional insulin delivery routes based on amidated pectin hydrogel matrix gel. We therefore investigated whether the application of pectin insulin (PI)-containing dermal patches of different insulin concentrations sustain controlled release of insulin into the bloodstream of streptozotocin (STZ)-induced diabetic rats with concomitant alleviation of diabetic symptoms in target tissues, most importantly, muscle and liver. Methods Oral glucose test (OGT) responses to PI dermal matrix patches (2.47, 3.99, 9.57, 16.80 µg/kg) prepared by dissolving pectin/insulin in deionised water and solidified with CaCl2 were monitored in diabetic rats given a glucose load after an 18-h fast. Short-term (5 weeks) metabolic effects were assessed in animals treated thrice daily with PI patches 8 hours apart. Animals treated with drug-free pectin and insulin (175 µg/kg, sc) acted as untreated and treated positive controls, respectively. Blood, muscle and liver samples were collected for measurements of selected biochemical parameters. Results After 5 weeks, untreated diabetic rats exhibited hyperglycaemia and depleted hepatic and muscle glycogen concentrations. Compared to untreated STZ-induced diabetic animals, OGT responses of diabetic rats transdermally applied PI patches exhibited lower blood glucose levels whilst short-term treatments restored hepatic and muscle glycogen concentrations. Plasma insulin concentrations of untreated diabetic rats were low compared with control non-diabetic rats. All PI treatments elevated plasma insulin concentrations of diabetic rats although the levels induced by high doses (9.57 and 16.80 µg/kg) were greater than those caused by low doses (2.47 and 3.99 µg/kg) but comparable to those in sc insulin treated animals. Conclusions The data suggest that the PI hydrogel matrix patch can deliver physiologically relevant amounts of pharmacologically active insulin. Novelty of the Work A new

  8. Single- and multiple-dose pharmacokinetics of a novel tetramethylpyrazine reservoir-type transdermal patch versus tetramethylpyrazine phosphate oral tablets in healthy normal volunteers, and in vitro/in vivo correlation.

    PubMed

    Shen, Teng; Xu, Huinan; Weng, Weiyu; Zhang, Jianfang

    2013-01-01

    A novel reservoir-type transdermal system of 2,3,5,6-tetramethylpyrazine (TMP) was developed containing eucalyptus oil as a penetration enhancer. The single and multiple-dose pharmacokinetic profiles of TMP administrated by TMP transdermal patch were characterized in healthy volunteers using an in vivo, randomized, open-label, two-way crossover design. 2,3,5,6-Tetramethylpyrazine phosphate (TMPP) oral tablets were chosen as reference. Following single/multiple oral administration of 200/100 mg TMPP tablets, a TMP C(max) of 1284/613.5 ng/mL was observed within 0.75 h. Single/multiple applications of the TMP patch yielded mean C(max) of 309/325 ng/mL at a median T(max) of 5/4 h, with steady state achieved at second application. The mean C(min) of the patch was 131±30.38 ng/mL, contrasting to nearly zero for the tablet. Multiple applications of patch produced an accumulative effect over single application. At steady state 250 mg/20 cm(2) TMP patch given daily provided comparable exposure to 100 mg TMPP tablets three times daily (3753.91 versus 3563.67 ng·h/mL). TMP tablets and patch yielded similar steady-state plasma concentrations: C(av) (148.48±51.27, 156.41±40.31 ng/mL). The results demonstrated that TMP patch can achieve a therapeutic effect that is comparable to oral administration, exhibited prolonged and sustained plasma levels, fewer drug fluctuations, lower adverse effects, more convenience, and improved patient compliance. In-vitro permeation through human skin demonstrated zero-order kinetics with the flux of 364 µg/cm(2)/h. The predicted C(av) (163.9 ng/mL) was in agreement with the observed C(av) (156.4 ng/mL). PMID:23514701

  9. Transdermal delivery: product and patent update.

    PubMed

    Gupta, Himanshu; Babu, R J

    2013-12-01

    Transdermal drug delivery is an attractive alternative to the oral and parenteral drug delivery. Drugs which are prone to first-pass metabolism can be delivered easily in small doses with sustained blood levels through this method. An update to available products along with a review of clinical trials and patents are discussed in this study. In this review, we have compiled 16 drugs, i.e. Buprenorphine, Clonidine, Estradiol, Fentanyl, Granisetron, Lidocaine, Methylphenidate, Nicotine, Nitroglycerin, Oxybutynin, Rivastigmine, Rotigotine, Scopolamine, Selegiline, Testosterone, Influenza virus vaccine (Microneedle) and covering about 22 marketed products on the transdermal system. We present instrumental information on them along with the compilation of current clinical trials on transdermal systems. We summarize the contents of patents granted in last 5 years under different pharmacological categories. This article serves, accordingly as a source of available information focused on transdermal drug delivery research. PMID:24025130

  10. Fentanyl Sublingual Spray

    MedlinePlus

    Fentanyl sublingual spray is used to treat breakthrough pain (sudden episodes of pain that occur despite round ... effects of the medication) to narcotic pain medications. Fentanyl is in a class of medications called narcotic ( ...

  11. Fentanyl Nasal Spray

    MedlinePlus

    Fentanyl nasal spray is used to treat breakthrough pain (sudden episodes of pain that occur despite round ... effects of the medication) to narcotic pain medications. Fentanyl is in a class of medications called narcotic ( ...

  12. Practice guidelines for transdermal opioids in malignant pain.

    PubMed

    Skaer, Tracy L

    2004-01-01

    Patients with moderate-to-severe malignancy-related pain require opioid pharmacotherapy. Many cancer patients continue to be prescribed subtherapeutic doses of pain medications resulting in undue suffering and diminished quality of life. Pain associated with malignancy and its treatment may exacerbate other symptoms associated with cancer, including nausea, fatigue, weakness, dyspnoea, constipation and impaired cognition. The choice of analgesic pharmacotherapy should be individualised and based on the intensity of pain reported by the patient, rather than its specific aetiology. When selecting pain management pharmacotherapy, the healthcare provider should consider the patient's pain level, activity level and any comorbid illness. Intolerable adverse effects, ineffective pain relief or a change in the patient's clinical status can dictate the need for a new pain management regimen. Healthcare providers must be able to readily quantify the relative analgesic potency when converting from one opioid to another or from one route of administration to another. Transdermal formulations of fentanyl and buprenorphine are effective pharmacotherapy that can be safely used for cancer patients with pain. However, clinicians need to be cognisant that the US/UK manufacturer's recommendations for equianalgesic dose administration of transdermal fentanyl may result in initial doses that produce subtherapeutic concentrations and unrelieved pain in some patients. A less conservative dose administration algorithm for transdermal fentanyl using a 2:1 (mg/day of oral morphine : microg/h of transdermal fentanyl) conversion ratio that considers both a review of the literature and clinical experience should help clinicians individualise cancer pain pharmacotherapy. PMID:15537367

  13. New formulations of fentanyl for acute pain management.

    PubMed

    Paech, M J; Bloor, M; Schug, S A

    2012-02-01

    Intravenous fentanyl citrate has stood the test of time as a valuable formulation for pain management. The desirable physicochemical properties of fentanyl have allowed the development of several alternative formulations for delivery using less invasive routes, for example, transmucosal (intranasal, oral buccal and oral sublingual) and transdermal. These new formulations have been applied to clinical settings in which rapid onset of analgesia is desired, using convenient but noninvasive methods. Recent commercialization of various formulations has been driven largely by the needs of cancer patients, for whom severe but self-limiting "breakthrough" pain is less suitably treated by parenteral or oral routes of opioid administration. However, these formulations are also used for acute analgesia in prehospital and in-hospital emergency department care, and for pediatric acute pain management. Finally, they are increasingly used by patients with chronic pain of nonmalignant origin, although there is considerable debate about their merit in this group. We searched the databases MEDLINE, PubMed, EMBASE, CINAHL and Cochrane up to October 2011, using search terms "fentanyl AND nasal; intranasal; transmucosal; buccal; sublingual; oral; inhaled; inhalation; transdermal". The characteristics of several formulations of fentanyl are reviewed, detailing their pharmacokinetics, pharmacodynamics and clinical experience with their use for acute pain management. PMID:22384452

  14. Progressive Change in Joint Degeneration in Patients with Knee or Hip Osteoarthritis Treated with Fentanyl in a Randomized Trial

    PubMed Central

    Fujii, Tatsuya; Takana, Koshi; Orita, Sumihisa; Inoue, Gen; Ochiai, Nobuyasu; Kuniyoshi, Kazuki; Aoki, Yasuchika; Ishikawa, Tetsuhiro; Miyagi, Masayuki; Kamoda, Hiroto; Suzuki, Miyako; Sakuma, Yoshihiro; Kubota, Gou; Oikawa, Yasuhiro; Inage, Kazuhide; Sainoh, Takeshi; Sato, Jun; Yamauchi, Kazuyo; Toyone, Tomoaki; Nakamura, Junichi; Kishida, Shunji; Takahashi, Kazuhisa

    2014-01-01

    Purpose Opioids improve pain from knee and hip osteoarthritis (OA) and decrease the functional impairment of patients. However, there is a possibility that opioids induce analgesia and suppress the physiological pain of OA in patients, thereby inducing the progression of OA changes in these patients. The purpose of the current study was to investigate the possibility of progressive changes in OA among patients using opioids. Materials and Methods Two hundred knee or hip OA patients were evaluated in the current prospective, randomized, active-controlled study. Patients were randomized 1:1:1 into three parallel treatment groups: loxoprofen, tramadol/acetaminophen, and transdermal fentanyl groups. Medication was administered for 12 weeks. Pain scores and progressive OA changes on X-ray films were evaluated. Results Overall, pain relief was obtained by all three groups. Most patients did not show progressive OA changes; however, 3 patients in the transdermal fentanyl group showed progressive OA changes during the 12 weeks of treatment. These 3 patients used significantly higher doses than others in the transdermal fentanyl group. Additionally, the average pain score for these 3 patients was significantly lower than the average pain score for the other patients in the transdermal fentanyl group. Conclusion Fentanyl may induce progressive changes in knee or hip OA during a relatively short period, compared with oral Non-Steroidal Anti-Inflammatory Drugs or tramadol. PMID:25048500

  15. Fentanyl Sublingual Spray

    MedlinePlus

    ... who are taking regularly scheduled doses of another narcotic (opiate) pain medication, and who are tolerant (used to the effects of the medication) to narcotic pain medications. Fentanyl is in a class of ...

  16. Relationship between the plasma fentanyl and serum 4β-hydroxycholesterol based on CYP3A5 genotype and gender in patients with cancer pain.

    PubMed

    Ishida, Takuya; Naito, Takafumi; Sato, Hikaru; Kawakami, Junichi

    2016-06-01

    This study aimed to evaluate the relationship between the concentrations of plasma fentanyl and serum 4β-hydroxycholesterol based on CYP3A5 genotype and gender in cancer patients. Thirty-three Japanese cancer patients treated with transdermal fentanyl were enrolled. The concentrations of plasma fentanyl and norfentanyl, and serum 4β-hydroxycholesterol and total cholesterol were determined at day 8 or later after starting the medication. The plasma fentanyl concentration was significantly higher in the CYP3A5*3/*3 group than in the *1 allele carrier group. The *3/*3 group had a lower metabolic ratio of fentanyl. The serum 4β-hydroxycholesterol concentration and its ratio to total cholesterol were significantly lower in the CYP3A5*3/*3 group than in the *1 allele carrier group. The concentrations of plasma fentanyl and serum 4β-hydroxycholesterol were significantly higher in women than in men. Gender did not affect the metabolic ratio of fentanyl or the concentration ratio of 4β-hydroxycholesterol. The plasma fentanyl concentration was not correlated with the serum 4β-hydroxycholesterol concentration, while the metabolic ratio of fentanyl was slightly correlated with the serum concentration ratio of 4β-hydroxycholesterol. In conclusion, CYP3A5*3 and gender affected the plasma fentanyl and serum 4β-hydroxycholesterol concentrations in cancer patients. However, the plasma disposition of fentanyl was not determined using the serum 4β-hydroxycholesterol concentration. PMID:27236640

  17. Transdermal innovations in diabetes management.

    PubMed

    Rao, Rekha; Mahant, Sheefali; Chhabra, Lovely; Nanda, Sanju

    2014-01-01

    Diabetes mellitus, an endocrine disorder affecting glucose metabolism, has been crippling mankind for the past two centuries. Despite the advancements in the understanding pertaining to its pathogenesis and treatment, the currently available therapeutic options are far from satisfactory. The growing diabetic population increases the gravity of the situation. The shortcomings of the conventional drug delivery systems necessitate the need to delve into other routes. On account of its merits over other routes, the transdermal approach has drawn the interest of the researchers around the world. The transdermal drug delivery systems are aimed to achieve therapeutic concentrations of the drug through skin. These systems are designed so that the drug can be delivered at a pre-determined and controlled rate. This makes it particularly conducive to treat chronic disorders like diabetes. Correspondingly, the adverse effects and inconvenience concomitant with oral and parentral route are circumvented. This article attempts to outline the development of transdermal drug delivery systems to optimize diabetes pharmacotherapy. It not only covers the transdermal approaches adopted to fine-tune insulin delivery, but also, discusses various transdermal drug delivery systems fabricated to improve the therapeutic performance of oral hypoglycaemic agents. Such formulations include the advanced drug delivery systems, namely, transferosomal gels, microemulsions, self-dissolving micropiles, nanoparticles, insulin pumps, biphasic lipid systems, calcium carbonate nanoparticles, lecithin nanoparticles; physical techniques such as iontophoresis and microneedles and, drugs formulated as transdermal patches. In addition to this, the authors have also shed light on the future prospects and patented and commercial formulations of antidiabetic agents. PMID:25418713

  18. Transdermal delivery of corticosterone in terrestrial amphibians.

    PubMed

    Wack, Corina L; Lovern, Matthew B; Woodley, Sarah K

    2010-12-01

    Stressors elicit allostatic responses that allow animals to cope with changing and challenging environments and also cause release of glucocorticoid hormones (GCs). Compared to other vertebrate classes, relatively little is known about amphibian behavioral and physiological responses to GCs. To understand the effects of elevated plasma GCs in amphibians, exogenous application of GCs is necessary, but traditional methods to elevate GCs require handling and/or anesthesia which themselves are stressors. A less invasive alternative successfully used in birds and reptiles utilizes transdermal delivery by applying GCs via a dermal patch. We asked whether dermal patches containing corticosterone (CORT, the main GC in amphibians) would elevate plasma CORT in terrestrial salamanders and frogs. We explored the use of the dermal patch to deliver CORT in an acute, sustained, and repeated manner. Patches adhered well to the amphibians' moist skin and were easily removed to regulate the time course of CORT delivery. Application of CORT treated patches elevated plasma CORT concentrations compared to vehicle patches in all species. Patches delivered physiological levels of plasma CORT in ecologically relevant time frames. Repeated application and removal of CORT patches were used to simulate exposure to repeated stressors. Application of patches did not represent a stressor because plasma CORT concentrations were similar between animals that received vehicle patches and untreated animals. Thus, transdermal delivery of GCs represents a potentially useful tool to better understand amphibian allostatic responses to stressors, and perhaps amphibian population declines. PMID:20850442

  19. Transdermal selegiline.

    PubMed

    Patkar, Ashwin A; Pae, Chi-Un; Zarzar, Michael

    2007-06-01

    Although older monoamine oxidase inhibitors (MAOIs) are effective in the treatment of depressive disorders, they are underutilized in clinical practice due to main concerns about interaction with tyramine-containing food, and side effects. Efforts to address these safety issues led to the development of a transdermal formulation of selegiline, called selegiline transdermal system (STS). STS has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of major depression. Transdermal administration of selegiline bypasses gastrointestinal absorption and first-pass metabolism. Therefore, STS permits inhibition of monoamine oxidase (MAO)-A and MAO-B enzymes in the brain while preserving the activity of MAO-A in the gastrointestinal system, thereby minimizing the risk of possible interactions with tyramine-rich foods. Tyramine challenge tests have confirmed that dietary modifications are not required with the 6 mg STS. The FDA has required dietary modifications with the 9 mg and 12 mg STS. Compared to oral administration, transdermal selegiline leads to sustained (minimal peak-trough fluctuations) plasma concentrations of the parent compound, increasing the amount of drug delivered to the brain. The efficacy of STS has been established in several short-term and one long-term randomized controlled trials. In clinical trials, application site reactions and insomnia were observed more frequently with STS than placebo. Rates of orthostatic hypotension, sexual dysfunction and weight gain were comparable between STS and placebo. STS is a new generation of MAOI with superior safety profile to older MAOIs. It increases the pharmacological options available to treat depressive disorders and may benefit patients with major depression with atypical features and resistant depression. It is important for health-care professionals to be informed about the properties of STS. PMID:17612708

  20. [Design of transdermal ultrasonophoresis equipment].

    PubMed

    Li, Liangcheng; Zhang, Yongshun; Li, Zhonghong

    2009-02-01

    The recent fast development in biotechnology has resulted in a large number of therapeutic biologicals coming in the foreground for clinical application. Transdermal drug delivery (TDD) is designed for patching the drug on the skin, and then the drug molecules permeate through the skin into the subcutaneous capillary vessels. However,very few drugs can be administered transdermally at the therapeutic levels to pass through the barrier of stratum corneum. Several physical and chemical methods are applied to improve the permeability of skin. Research result shows that the low-frequency ultrasonic technique can extraordinarily increase the rate of permeation. As a result, it is becoming one of the potential methods that serve as the substitutes for traditional methods. In this paper is presented a type of equipment based on MSP430. The principle of design, the structure of hardware, and the applied function in this area are described. PMID:19334582

  1. Comparative enhancing effects of electret with chemical enhancers on transdermal delivery of meloxicam in vitro

    NASA Astrophysics Data System (ADS)

    Cui, L. L.; Hou, X. M.; Jiang, J.; Li, G. D.; Liang, Y. Y.; Xin, X.

    2008-12-01

    Electret offers enhancing effect in transdermal drug delivery for altering of the arrangement of lipid molecules in the stratum corneum, forming many transient permeable apertures and enhancing the transdermal drug delivery. In this paper, meloxicam patch formulations were developed to make the comparative study of transdermal drug delivery between electret and chemical enhancers. Patches were made into control, electret, chemical enhancer and electret with chemical enhancer ones, according to the preparation procedure. The electret combined with chemical enhancer patch was designed to probe the incorporation between electret and chemical enhancer in transdermal drug delivery. The meloxicam release from the patch was found to increase in order of blank, chemical enhancer, electret and electret with chemical enhancer patch, in general.

  2. Current and emerging formulation strategies for the effective transdermal delivery of HIV inhibitors

    PubMed Central

    Ham, Anthony S; Buckheit, Robert W

    2015-01-01

    Current and emerging formulation strategies for skin permeation are poised to open the transdermal drug delivery to a broader range of small molecule compounds that do not fit the traditional requirements for successful transdermal drug delivery, allowing the development of new patch technologies to deliver antiretroviral drugs that were previously incapable of being delivered through transdermal means. Transdermal drug delivery offers several distinct advantages over traditional dosage forms. Current antiretroviral drugs used for the treatment of HIV infection include a variety of highly active small molecule compounds with significantly limited skin permeability, and thus new and novel means of enhancing transport through the skin are needed. Current and emerging formulation strategies are poised to open the transdermal drug delivery to a broader range of compounds that do not fit the traditional requirements for successful transdermal drug delivery, allowing the development of new patch technologies to deliver antiretroviral drugs that were previously incapable of being delivered through transdermal means. Thus, with continuing research into skin permeability and patch formulation strategies, there is a large potential for antiretroviral transdermal drug delivery. PMID:25690088

  3. Fatal Intoxication with Acetyl Fentanyl.

    PubMed

    Cunningham, Susan M; Haikal, Nabila A; Kraner, James C

    2016-01-01

    Among the new psychoactive substances encountered in forensic investigations is the opioid, acetyl fentanyl. The death of a 28-year-old man from recreational use of this compound is reported. The decedent was found in the bathroom of his residence with a tourniquet secured around his arm and a syringe nearby. Postmortem examination findings included marked pulmonary and cerebral edema and needle track marks. Toxicological analysis revealed acetyl fentanyl in subclavian blood, liver, vitreous fluid, and urine at concentrations of 235 ng/mL, 2400 ng/g, 131 ng/mL, and 234 ng/mL, respectively. Acetyl fentanyl was also detected in the accompanying syringe. Death was attributed to recreational acetyl fentanyl abuse, likely through intravenous administration. The blood acetyl fentanyl concentration is considerably higher than typically found in fatal fentanyl intoxications. Analysis of this case underscores the need for consideration of a wide range of compounds with potential opioid-agonist activity when investigating apparent recreational drug-related deaths. PMID:26389815

  4. Navigating sticky areas in transdermal product development.

    PubMed

    Strasinger, Caroline; Raney, Sam G; Tran, Doanh C; Ghosh, Priyanka; Newman, Bryan; Bashaw, Edward D; Ghosh, Tapash; Shukla, Chinmay G

    2016-07-10

    The benefits of transdermal delivery over the oral route to combat such issues of low bioavailability and limited controlled release opportunities are well known and have been previously discussed by many in the field (Prausnitz et al. (2004) [1]; Hadgraft and Lane (2006) [2]). However, significant challenges faced by developers as a product moves from the purely theoretical to commercial production have hampered full capitalization of the dosage forms vast benefits. While different technical aspects of transdermal system development have been discussed at various industry meetings and scientific workshops, uncertainties have persisted regarding the pharmaceutical industry's conventionally accepted approach for the development and manufacturing of transdermal systems. This review provides an overview of the challenges frequently faced and the industry's best practices for assuring the quality and performance of transdermal delivery systems and topical patches (collectively, TDS). The topics discussed are broadly divided into the evaluation of product quality and the evaluation of product performance; with the overall goal of the discussion to improve, advance and accelerate commercial development in the area of this complex controlled release dosage form. PMID:27117457

  5. Varying the Wear Time of the Methylphenidate Transdermal System in Children with Attention-Deficit/Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Wilens, Timothy E.; Boellner, Samuel W.; Lopez, Frank A.; Turnbow, John M.; Wigal, Sharon B.; Childress, Ann C.; Abikoff, Howard B.; Manos, Michael J.

    2008-01-01

    A study investigated the impact of variable wear times of the methylphenidate transdermal system in children with attention-deficit/hyperactivity disorder (ADHD). It was concluded that duration of medication effect was directly related to the wear time of the methylphenidate transdermal system patch.

  6. Pharmacokinetic interaction of intravenous fentanyl with ketoconazole.

    PubMed

    Ziesenitz, Victoria C; König, Sonja K; Mahlke, Nina S; Skopp, Gisela; Haefeli, Walter E; Mikus, Gerd

    2015-06-01

    Fentanyl is primarily metabolized by CYP3A, but has also been suggested to act as a weak inhibitor of CYP3A. We investigated the influence of CYP3A inhibition by ketoconazole on the pharmacokinetics of intravenously administered fentanyl and the effect of fentanyl on CYP3A activity. A prospective, open-label, randomized, monocentre, crossover study was conducted in 16 healthy volunteers. They received fentanyl alone (5 microgram per kilogram) or fentanyl plus ketoconazole (200 milligram orally B.I.D. over 2 days). Naloxone (2 × 0.2 milligram i.v.) was given simultaneously with fentanyl to mitigate any opioid effect. Midazolam was administered as a CYP3A probe drug. Fentanyl and its metabolites were quantified by LC/MS/MS in blood and urine samples obtained over 24 hour. Exposure of fentanyl (AUC0- ∞ ) was significantly increased to 133% and systemic clearance was reduced to 78% by ketoconazole, norfentanyl formation was significantly delayed and partial metabolic clearance decreased to 18%. Fentanyl had no influence on midazolam exposure and CYP3A activity whereas ketoconazole decreased CYP3A activity to 13%. Although fentanyl N-dealkylation is substantially inhibited by ketoconazole, exposure of fentanyl itself increased by one third only. Clinically fentanyl dosage adjustments may become necessary when ketoconazole or other strong CYP3A inhibitors are given simultaneously. Fentanyl itself does not influence CYP3A activity. PMID:25651378

  7. Transdermal delivery of contraceptives.

    PubMed

    Friend, D R

    1990-01-01

    Contraceptive agents are administered to the body through a variety of routes. Research has recently been directed at examining the transdermal route for systemic delivery of contraceptive agents, including estrogens and progestins. The transdermal route has several potential advantages over the other routes of administration: (1) improved compliance, (2) once-weekly administration, (3) delivery is easily terminated, and (4) some side effects can be alleviated based on more constant delivery rates. This article reviews the permeability of skin toward contraceptive steroids and how skin permeability is evaluated. The metabolism of contraceptive steroids is also considered. Transdermal delivery systems used to deliver contraceptives are presented, followed by a detailed discussion of several delivery systems for specific contraceptive agents such as levonorgestrel and estradiol. The potential problem of skin irritation is presented as it relates to transdermal contraceptive delivery systems, all of which will be worn chronically. PMID:2272099

  8. [Transdermal Delivery of NSAIDs].

    PubMed

    Nakajima, Takehisa; Makino, Kimiko

    2015-11-01

    Skin has been studied as administration site of drug for its systemic effects, since systemic therapeutic agents can be delivered for long time with a controlled ratio, escaping from the first pass effect by liver by the transdermal delivery, which can decrease the dosage form. The low permeability of drug molecules through stratum corneum has been the limiting factor for developing transdermal delivery system of therapeutic agents. To enhance the permeability of drug molecules, many studies have been reported. PMID:26689064

  9. Transdermal Delivery of Drugs with Microneedles—Potential and Challenges

    PubMed Central

    Ita, Kevin

    2015-01-01

    Transdermal drug delivery offers a number of advantages including improved patient compliance, sustained release, avoidance of gastric irritation, as well as elimination of pre-systemic first-pass effect. However, only few medications can be delivered through the transdermal route in therapeutic amounts. Microneedles can be used to enhance transdermal drug delivery. In this review, different types of microneedles are described and their methods of fabrication highlighted. Microneedles can be fabricated in different forms: hollow, solid, and dissolving. There are also hydrogel-forming microneedles. A special attention is paid to hydrogel-forming microneedles. These are innovative microneedles which do not contain drugs but imbibe interstitial fluid to form continuous conduits between dermal microcirculation and an attached patch-type reservoir. Several microneedles approved by regulatory authorities for clinical use are also examined. The last part of this review discusses concerns and challenges regarding microneedle use. PMID:26131647

  10. Transdermal Estradiol Treatment for Postpartum Depression: A Pilot, Randomized Trial.

    PubMed

    Wisner, Katherine L; Sit, Dorothy K Y; Moses-Kolko, Eydie L; Driscoll, Kara E; Prairie, Beth A; Stika, Catherine S; Eng, Heather F; Dills, John L; Luther, James F; Wisniewski, Stephen R

    2015-08-01

    Postpartum depression occurs in 14.5% of women in the first 3 months after birth. This study was an 8-week acute phase randomized trial with 3 cells (transdermal estradiol [E2], sertraline [SERT], and placebo [PL]) for the treatment of postpartum major depressive disorder. However, the study was stopped after batch analysis revealed that the E2 serum concentrations were lower than prestudy projections. This paper explores our experiences that will inform future investigations of therapeutic E2 use. Explanations for the low E2 concentrations were as follows: (1) study patch nonadhesion, which did not explain the low concentrations across the entire sample. (2) Ineffective transdermal patch preparations, although 2 different patch preparations were used and no significant main effect of patch type on E2 concentrations was found. (3) Obesity, at study entry, E2-treated women had body mass index of 32.9 (7.4) (mean [SD]). No pharmacokinetic data comparing E2 concentrations from transdermal patches in obese women versus normal weight controls are available. (4) Induction of cytochrome P450 (CYP450) 3A4 and other E2 elimination pathways in pregnancy. CYP4503A4 is induced in pregnancy and is a pathway for the metabolism of E2. Conversion to estrone and phase II metabolism via glucuronidation and sulfation, which also increase in pregnancy, are routes of E2 elimination. The time required for these pathways to normalize after delivery has not been elucidated. The observation that transdermal E2 doses greater than 100 μg/d did not increase serum concentrations was unexpected. Another hypothesis consistent with this observation is suppression of endogenous E2 secretion with increasing exogenous E2 dosing. PMID:26061609

  11. Transdermal Estradiol Treatment for Postpartum Depression: A Pilot Randomized Trial

    PubMed Central

    Wisner, Katherine L.; Sit, Dorothy K.Y.; Moses-Kolko, Eydie L.; Driscoll, Kara E.; Prairie, Beth; Stika, Catherine S.; Eng, Heather F.; Dills, John L; Luther, James F.; Wisniewski, Stephen R.

    2015-01-01

    Postpartum depression occurs in 14.5% of women in the first three months after birth. This study was an 8 week acute phase randomized trial with three cells (transdermal estradiol (E2), sertraline, and placebo) for the treatment of postpartum major depressive disorder. However, the study was stopped after batch analysis revealed that the E2 serum concentrations were lower than pre-study projections. This paper explores our experiences that will inform future investigations of therapeutic E2 use. Explanations for the low E2 concentrations were: 1) Study patch non-adhesion, which did not explain the low concentrations across the entire sample. 2) Ineffective transdermal patch preparations, although two different patch preparations were used and no significant main effect of patch type on E2 concentrations was found. 3) Obesity, at study entry, E2-treated women had mean ± SD BMI=32.9 ±7.4. No pharmacokinetic data comparing E2 concentrations from transdermal patches in obese women vs. normal weight controls are available. 4) Induction of Cytochrome P450 (CYP450) 3A4 and other E2 elimination pathways in pregnancy. CYP4503A4 is induced in pregnancy and is a pathway for the metabolism of E2. Conversion to estrone and Phase II metabolism via glucuronidation and sulfation, which also increase in pregnancy, are routes of E2 elimination. The time required for these pathways to normalize after delivery has not been elucidated. The observation that transdermal E2 doses greater than 100 mcg/day did not increase serum concentrations was unexpected. Another hypothesis consistent with this observation is suppression of endogenous E2 secretion with increasing exogenous E2 dosing. PMID:26061609

  12. Salmon Patch

    MedlinePlus

    ... the head. Salmon patches are different from port-wine stains (discussed as a separate topic) in that ... difference between a salmon patch and a port-wine stain. In the past, port-wine stains and ...

  13. Stroke Mimic Secondary to IV Fentanyl Administration.

    PubMed

    Uhegwu, Nnamdi; Bashir, Asif; Dababneh, Haitham; Hussain, Mohammed; Misthal, Sara; Mocco, J Duffy

    2015-02-01

    Fentanyl is a potent opioid used commonly in acute care because of its rapid onset and short duration of action. It has fewer side effects when compared with commonly available opioids, such as morphine and hydromorphine. We report an unusual side effect of transient aphasia following fentanyl administration. A 61-year-old female presented for an elective embolization of a periophthalmic artery aneurysm. She developed immediate episodes of aphasia on two separate occasions following administration of intravenous (IV) fentanyl. The high lipid solubility explains the rapid onset of action of fentanyl as it rapidly passes through the blood-brain barrier and through cell membranes. Immediately following the administration of fentanyl, the patient developed aphasia. There were no other clinical or neurological imaging findings that could account for these symptoms. We believe that aphasia may be an unusual side effect of fentanyl, and it is something clinicians should be aware of. PMID:25825627

  14. Effect of Transdermal Teriparatide Administration on Bone Mineral Density in Postmenopausal Women

    PubMed Central

    Cosman, Felicia; Lane, Nancy E.; Bolognese, Michael A.; Zanchetta, Jose R.; Garcia-Hernandez, Pedro A.; Sees, Karen; Matriano, James A.; Gaumer, Kim; Daddona, Peter E.

    2010-01-01

    Context: Treatment of osteoporosis with an anabolic agent, teriparatide [human PTH 1-34 (TPTD)], is effective in reducing incident fractures, but patient resistance to daily sc injections has limited its use. A novel transdermal patch, providing a rapid, pulse delivery of TPTD, may provide a desirable alternative. Objective: The aim of the study was to determine the safety and efficacy of a novel transdermal TPTD patch compared to placebo patch and sc TPTD 20-μg injection in postmenopausal women with osteoporosis. Design: Our study consisted of 6-month, randomized, placebo-controlled, positive control, multidose daily administration. Patients: We enrolled 165 postmenopausal women (mean age, 64 yr) with osteoporosis. Interventions: A TPTD patch with a 20-, 30-, or 40-μg dose or a placebo patch was self-administered daily for 30-min wear time, or 20 μg of TPTD was injected daily. Outcomes: The primary efficacy measure was mean percentage change in lumbar spine bone mineral density (BMD) from baseline at 6 months. Results: TPTD delivered by transdermal patch significantly increased lumbar spine BMD vs. placebo patch in a dose-dependent manner at 6 months (P < 0.001). TPTD 40-μg patch increased total hip BMD compared to both placebo patch and TPTD injection (P < 0.05). Bone turnover markers (procollagen type I N-terminal propeptide and C-terminal cross-linked telopeptide of type I collagen) increased from baseline in a dose-dependent manner in all treatment groups and were all significantly different from placebo patch (P < 0.001). All treatments were well tolerated, and no prolonged hypercalcemia was observed. Conclusion: Transdermal patch delivery of TPTD in postmenopausal women with osteoporosis for 6 months is safe and effective in increasing lumbar spine and total hip BMD. PMID:19858319

  15. Transdermal drug delivery

    PubMed Central

    Prausnitz, Mark R.; Langer, Robert

    2009-01-01

    Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, non-cavitational ultrasound and iontophoresis have also resulted in clinical products; the ability of iontophoresis to control delivery rates in real time provides added functionality. Third-generation delivery systems target their effects to skin’s barrier layer of stratum corneum using microneedles, thermal ablation, microdermabrasion, electroporation and cavitational ultrasound. Microneedles and thermal ablation are currently progressing through clinical trials for delivery of macromolecules and vaccines, such as insulin, parathyroid hormone and influenza vaccine. Using these novel second- and third-generation enhancement strategies, transdermal delivery is poised to significantly increase impact on medicine. PMID:18997767

  16. The Use of Transdermal Buprenorphine in Complex Regional Pain Syndrome: A Report of Two Cases.

    PubMed

    Onofrio, Sarah; Vartan, Christine M; Nazario, Mitchell; DiScala, Sandra; Cuevas-Trisan, Ramon; Melendez-Benabe, John

    2016-06-01

    Management of complex regional pain syndrome (CRPS) can be challenging. Various pharmacological approaches have produced mixed results. Buprenorphine activates mu-opioid receptors and antagonizes kappa and delta receptors, acts at N-methyl-d-aspartate (NMDA) receptor, and is an orphan-related ligand-1 receptor agonist. It is available in transdermal patches that last for up to 7 days. This report describes two patients with refractory CRPS who were treated with transdermal buprenorphine. The patients experienced approximately 50% reduction in pain intensity scores. Application site rash that occurred was managed with topical steroid spray used before applying the patch. PMID:27172230

  17. Perspectives on Transdermal Electroporation.

    PubMed

    Ita, Kevin

    2016-01-01

    Transdermal drug delivery offers several advantages, including avoidance of erratic absorption, absence of gastric irritation, painlessness, noninvasiveness, as well as improvement in patient compliance. With this mode of drug administration, there is no pre-systemic metabolism and it is possible to increase drug bioavailability and half-life. However, only a few molecules can be delivered across the skin in therapeutic quantities. This is because of the hindrance provided by the stratum corneum. Several techniques have been developed and used over the last few decades for transdermal drug delivery enhancement. These include sonophoresis, iontophoresis, microneedles, and electroporation. Electroporation, which refers to the temporary perturbation of the skin following the application of high voltage electric pulses, has been used to increase transcutaneous flux values by several research groups. In this review, transdermal electroporation is discussed and the use of the technique for percutaneous transport of low and high molecular weight compounds described. This review also examines our current knowledge regarding the mechanisms of electroporation and safety concerns arising from the use of this transdermal drug delivery technique. Safety considerations are especially important because electroporation utilizes high voltage pulses which may have deleterious effects in some cases. PMID:26999191

  18. Perspectives on Transdermal Electroporation

    PubMed Central

    Ita, Kevin

    2016-01-01

    Transdermal drug delivery offers several advantages, including avoidance of erratic absorption, absence of gastric irritation, painlessness, noninvasiveness, as well as improvement in patient compliance. With this mode of drug administration, there is no pre-systemic metabolism and it is possible to increase drug bioavailability and half-life. However, only a few molecules can be delivered across the skin in therapeutic quantities. This is because of the hindrance provided by the stratum corneum. Several techniques have been developed and used over the last few decades for transdermal drug delivery enhancement. These include sonophoresis, iontophoresis, microneedles, and electroporation. Electroporation, which refers to the temporary perturbation of the skin following the application of high voltage electric pulses, has been used to increase transcutaneous flux values by several research groups. In this review, transdermal electroporation is discussed and the use of the technique for percutaneous transport of low and high molecular weight compounds described. This review also examines our current knowledge regarding the mechanisms of electroporation and safety concerns arising from the use of this transdermal drug delivery technique. Safety considerations are especially important because electroporation utilizes high voltage pulses which may have deleterious effects in some cases. PMID:26999191

  19. The use of polymers for dermal and transdermal delivery.

    PubMed

    Valenta, Claudia; Auner, Barbara G

    2004-09-01

    The use of polymers for skin preparations is manifold. Requirements of such polymers are dependent on the formulation types. The most applied polymers on skin belong to various classes, for example to cellulose derivatives, chitosan, carageenan, polyacrylates, polyvinylalcohol, polyvinylpyrrolidone and silicones. They are gelating agents, matrices in patches and wound dressings, anti-nucleants and penetration enhancers. Correlations between commercially available products and results of new scientific investigations are often difficult or not possible, because of the lack of comparative data especially for transdermal patches. Finally, two promising future trends of polymeric systems, gene delivery and tissue engineering, are discussed. PMID:15296955

  20. An update on the use of transdermal oxybutynin in the management of overactive bladder disorder

    PubMed Central

    Cohn, Joshua A.; Brown, Elizabeth T.; Reynolds, W. Stuart; Kaufman, Melissa R.; Milam, Douglas F.; Dmochowski, Roger R.

    2016-01-01

    Antimuscarinic medications are used to treat nonneurogenic overactive bladder refractory to nonpharmacologic therapy. Side effects such as dry mouth, constipation, blurred vision, dizziness, and impaired cognition limit the tolerability of therapy and are largely responsible for high discontinuation rates. Oxybutynin is a potent muscarinic receptor antagonist whose primary metabolite after first-pass hepatic metabolism is considered largely responsible for its associated anticholinergic side effects. Transdermal administration of medications bypasses hepatic processing. Specifically with oxybutynin, whose low molecular weight permits transdermal administration, bioavailability of the parent drug with oral administration is less than 10%, whereas with transdermal delivery is a minimum of 80%. The result has been an improved side effect profile in multiple clinical trials with maintained efficacy relative to placebo; however, the drug may still be discontinued by patients due to anticholinergic side effects and application site reactions. Transdermal oxybutynin is available as a patch that is changed every 3–4 days, a gel available in individual sachets, or via a metered-dose pump that is applied daily. The transdermal patch was briefly available as an over-the-counter medication for adult women, although at this time all transdermal formulations are available by prescription only. PMID:27034721

  1. Patch tests*

    PubMed Central

    Lazzarini, Rosana; Duarte, Ida; Ferreira, Alessandra Lindmayer

    2013-01-01

    Patch tests were introduced as a diagnostic tool in the late nineteenth century. Since then, they have improved considerably becoming what they are today. Patch tests are used in the diagnostic investigation of contact dermatitis worldwide. Batteries or series previously studied and standardized should be used in patch testing. The methodology is simple, but it requires adequate training for the results to be correctly interpreted and used. Despite having been used for over a century, it needs improvement like all other diagnostic techniques in the medical field. PMID:24474094

  2. Sumatriptan iontophoretic transdermal system for the acute treatment of migraine.

    PubMed

    Vikelis, Michail; Mitsikostas, Dimos D; Rapoport, Alan M

    2014-03-01

    SUMMARY We will describe the pharmacokinetic profile, clinical efficacy and safety data of the sumatriptan iontophoretic transdermal system (Zecuity®, NuPathe Inc., PA, USA), recently approved for the acute treatment of migraine with or without aura in adults, by the US FDA. This transdermal system utilizes a low-level electrical current to deliver sumatriptan transdermally and circumvents the GI tract. Pharmacokinetic studies have shown that iontophoretic delivery of sumatriptan achieves detectable plasma concentrations 15 min after activation with a maximum mean serum concentration of 22 ng/ml. A randomized, double-blind, controlled clinical trial demonstrated minimal triptan-related side effects and superior efficacy versus placebo. The pain-free rate at 2 h postdose was 18% of patients applying the sumatriptan patch versus 9% using the placebo (p = 0.0092). This sumatriptan transdermal system may be a good choice for migraineurs with severe nausea or vomiting, those with intolerable triptan-related adverse events and/or those not responding optimally to oral medications. PMID:24641436

  3. Fentanyl-induced asystole in two dogs.

    PubMed

    Jang, M; Son, W-G; Lee, I

    2015-06-01

    Fentanyl is used in small animals for perioperative analgesia during anaesthesia. Severe bradycardia and asystole were observed on bolus administration of a 3 µg/kg loading dose of fentanyl in two dogs under isoflurane anaesthesia. Premedication with 10 µg/kg glycopyrrolate did not prevent asystole in the first case; and although bradycardia was treated with 5 µg/kg glycopyrrolate administered intravenously in the second case, the heart rate continuously decreased and asystole subsequently developed. Asystole in both cases was quickly corrected by intravenous administration of 0 · 04 mg/kg atropine and closed chest compressions. This case report describes asystole induced by fentanyl administration in isoflurane anaesthetised dogs. Atropine was more effective than glycopyrrolate in the treatment of fentanyl-induced asystole. PMID:25599659

  4. Transdermal Nicotine During Cue Reactivity in Adult Smokers With and Without Anxiety Disorders

    PubMed Central

    Morissette, Sandra B.; Gulliver, Suzy Bird; Kamholz, Barbara W.; Spiegel, David A.; Tiffany, Stephen T.; Barlow, David H.

    2012-01-01

    Transdermal nicotine almost doubles tobacco cessation rates; however little is known about what happens to smokers during the quit process when they are wearing the nicotine patch and confronted with high-risk smoking triggers. This is particularly important for smokers with psychological disorders who disproportionately represent today’s smokers and have more trouble quitting. Using a mixed between- and within-subjects design, smokers with anxiety disorders (n = 61) and smokers without any current Axis I disorders (n = 38) received transdermal nicotine (21 mg) or a placebo patch over two assessment days separated by 48 hours. Urge to smoke was evaluated during a 5-hour patch absorption period (reflecting general smoking deprivation) and during imaginal exposure to theoretically high-risk triggers containing smoking cues, anxiety cues, both, or neutral cues. No differences were observed between smokers with and without anxiety disorders. Significant Patch X Time and Patch X Cue Content interactions were found. Both patch conditions experienced an increase in urge during the deprivation period, but post-absorption urge was significantly higher in the placebo condition, suggesting that transdermal nicotine attenuated the degree to which urge to smoke increased over time. During the cue reactivity trials, when participants received the nicotine patch, they experienced significantly lower urge in response to both smoking-only and neutral cues, but not when anxiety cues were present (alone or in combination with smoking cues). These data suggest that transdermal nicotine alleviates urge only under certain circumstances, and that adjunctive interventions are likely necessary to address smoking urges in response to spikes in distress among smokers trying to quit. PMID:22686966

  5. Rotigotine: the first new chemical entity for transdermal drug delivery.

    PubMed

    McAfee, Donald A; Hadgraft, Jonathan; Lane, Majella E

    2014-11-01

    Rotigotine is the first, and to date, the only new chemical entity to be formulated for transdermal delivery. Although first approved for the management of Parkinson's disease in Europe in 2007 and Restless Leg Syndrome in 2008, the story of rotigotine began more than twenty years earlier. In this review we outline the historical development of this molecule and its route to licensed medicine status. It has very favourable physicochemical properties for transdermal delivery but it took a significant period to develop from concept to market. The stability problems which led to the temporary withdrawal of the patch are examined and the major clinical studies demonstrating efficacy and safety are outlined. Alternative new therapeutic modalities are also considered. PMID:25173087

  6. Transdermal absorption of memantin--effect of chemical enhancers, iontophoresis, and role of enhancer lipophilicity.

    PubMed

    del Rio-Sancho, S; Serna-Jiménez, C E; Calatayud-Pascual, M A; Balaguer-Fernández, C; Femenía-Font, A; Merino, V; López-Castellano, A

    2012-09-01

    The transdermal administration of memantine may have advantages with respect to oral therapy when treating advanced stages of Alzheimer's disease. With the ultimate objective of administrating memantine through a transdermal patch, the absorption of the drug across skin was evaluated by means of in vitro permeation studies. The effect of several chemical enhancers was studied in order to enhance percutaneous absorption of the memantine. The iontophoretic transdermal transport of memantine hydrochloride using a current density of 0.5 mA/cm(2) was also investigated. Results demonstrated that pre-treatment of the skin with R-(+)-limonene, laurocapram, decenoic acid, or oleic acid produced a statistically significant increment in the transdermal flux of memantine hydrochloride with respect to the control. Iontophoresis exhibited the greatest ability to enhance the flux of drug with respect to the control; nevertheless, the results obtained with R-(+)-limonene indicate that this compound could be of great use as a percutaneous enhancer in a memantine transdermal delivery system. In this study, the relationship between enhancement activity and lipophilicity was also studied. Satisfactory correlations have been obtained between the optimum lipophilicity of the enhancer and n-octanol/water partition coefficients of drugs. This relationship is a very useful tool that could allow to reduce time and to optimize the selection of appropriate enhancers for transdermal formulations. PMID:22732268

  7. Cutaneous pharmacodynamics of transdermally delivered isosorbide dinitrate.

    PubMed

    Hori, M; Ohtsuka, S; Sunami, M; Guy, R H; Maibach, H I

    1990-12-01

    Laser doppler velocimetry (LDV) has been used to assess the cutaneous pharmacodynamics of isosorbide dinitrate (ISDN) following transdermal delivery of the drug from prototypal patches. The delivery systems, which were saturated with ISDN, (a) produced various degrees of skin occlusion and (b) spanned a six-fold range of adhesiveness. The patches were applied to the ventral forearm skin of 10 healthy volunteers and the local ISDN-induced increase in local skin blood flow was determined using LDV by locating the probe in a central hole in the delivery system. Measurements were made for 1.5 hr and the pharmacodynamics were quantified by (i) the maximum LDV response and (ii) the area under the LDV response versus time curve. These parameters were not sensitive to patch occlusivity. They were significantly (P less than 0.01) dependent on patch adhesiveness, though, and decreased with increasing adhesion. Although this observation suggested that ISDN diffusion through the adhesive could determine, at least in part, the rate of drug delivery, it was subsequently demonstrated that ISDN release (in vitro, into a perfect "sink") was unaffected by the level of cross-linking in the adhesive polymer. Because the drug was present in all systems at unit thermodynamic activity, these results cannot be explained on the basis of altered ISDN partitioning at the device-stratum corneum interface. We speculate that the in vivo-in vitro discrepancy may be due to the efficiency of skin contact achieved by different adhesives: that is, the more adhesive, less flexible systems make poorer contact with the skin surface, thereby decreasing the effective surface area of drug delivery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2095569

  8. Development of Mesophasic Microreservoir-Based Transdermal Drug Delivery System of Propranolol

    PubMed Central

    Omray, L. K.; Kohli, S.; Khopade, A. J.; Patil, S.; Gajbhiye, Asmita; Agrawal, G. P.

    2008-01-01

    The mesophasic microreservoir comprises lyotrophic liquid crystals. The liquid crystals were prepared of Brij-35, cetosteryl alcohol and propranolol and evaluated for parameters viz. anisotropy, size and size distribution and drug entrapment efficiency. Subsequent to this liquid crystals based transdermal drug delivery system (TDS) was prepared by incorporating liquid crystals in previously prepared matrix based transdermal patch and evaluated for stability studies like temperature, humidity and aging. The system was also studied for tensile strength, moisture content, water vapor transmission, drug content, anisotropy and In vitro drug release studies. PMID:21394252

  9. Pharmacokinetics of subcutaneous fentanyl in Greyhounds.

    PubMed

    KuKanich, Butch

    2011-11-01

    The purpose of the study was to describe the pharmacokinetics of subcutaneous fentanyl (15μg/kg) in six healthy Greyhound dogs. Fentanyl plasma concentrations were determined by a liquid chromatography with mass spectrometry method. Non-compartmental pharmacokinetic analysis was used. Fentanyl was rapidly absorbed with a mean peak concentration (C(MAX)) of 3.56ng/mL at 0.24h. The mean terminal half-life, volume of distribution per bioavailability, and clearance per bioavailability were 2.97h, 7.09L/kg, 27.60mL/min/kg, respectively. Pain occurred on injection in all six dogs, but addition of 8.4% sodium bicarbonate (1mL per 20mL fentanyl) resulted in no pain on injection in 3/3 dogs but similar C(MAX) values. The subcutaneous route may be an alternative route of fentanyl administration if intravenous administration is not practical. PMID:21388844

  10. What if the Women's Health Initiative had used transdermal estradiol and oral progesterone instead?

    PubMed

    Simon, James A

    2014-07-01

    The author considers hypothetical comparisons between oral conjugated equine estrogens and transdermal estradiol and between oral medroxyprogesterone acetate and oral micronized progesterone for their effects on four primary outcomes of the Women's Health Initiative (WHI): cardiovascular disease risk, cerebrovascular disease risk, venous thromboembolism risk, and breast cancer risk. Although the discussion in this article focuses on transdermal estradiol delivered through patches, gels, or lotions, it could be broadened to include all forms of nonoral estrogen administration. After a brief review of the WHI and a survey of the relevant literature in which the safety of these various hormone therapies is assessed or compared, the author uses statistical methods to ascertain the attributable risk of venous thromboembolism for transdermal estradiol versus oral hormone therapy and imputes those risks into the WHI primary outcomes. PMID:24398406

  11. Programmable Transdermal Clonidine Delivery through Voltage Gated Carbon Nanotube Membranes

    PubMed Central

    Strasinger, Caroline; Paudel, Kalpana S; Wu, Ji; Hammell, Dana; Pinninti, Raghotham R.; Hinds, Bruce; Stinchcomb, Audra

    2014-01-01

    Oral dosage forms and traditional transdermal patches are inadequate for complex clonidine therapy dosing schemes, because of the variable dose/flux requirement for the treatment of opioid withdrawal symptoms. The purpose of this study was to evaluate the in vitro transdermal flux changes of clonidine in response to alterations in carbon nanotube (CNT) delivery rates by applying various electrical bias. Additional skin diffusion studies were carried out to demonstrate the therapeutic feasibility of the system. This study demonstrated that application of a small electrical bias (-600mV) to the CNT membrane on the skin resulted in a 4.7-fold increase in clonidine flux as compared to no bias (0mV) application. The high and low clonidine flux values were very close to the desired variable flux of clonidine for the treatment of opioid withdrawal symptoms. Therapeutic feasibility studies demonstrated that CNT membrane served as the rate limiting step to clonidine diffusion and lag and transition times were suitable for the clonidine therapy. Skin elimination studies revealed that clonidine depletion from the skin would not negatively affect clonidine therapy. Overall, this study showed that clonidine administration difficulties associated with the treatment of opiate withdrawal symptoms can be reduced with the programmable CNT membrane transdermal system. PMID:24788096

  12. Effect of iontophoresis on in vitro transdermal absorption of almotriptan.

    PubMed

    Calatayud-Pascual, M A; Balaguer-Fernández, C; Serna-Jiménez, C E; Del Rio-Sancho, S; Femenía-Font, A; Merino, V; López-Castellano, A

    2011-09-15

    The aim of the present work was to characterize the in vitro transdermal absorption of almotriptan through pig ear skin. The passive diffusion of almotriptan malate and its iontophoretic transport were investigated using current densities of 0.25 and 0.50mA/cm(2). In vitro iontophoresis experiments were conducted on diffusion cells with an agar bridge without background electrolytes in the donor compartment. Although both current densities applied produced a statistically significant increment with respect to passive permeation of almotriptan (p<0.01), that of 0.50mA/cm(2) proved to be the best experimental condition for increasing the transport of almotriptan across the skin. Under these experimental conditions, the transdermal flux of the drug increased 411-fold with respect to passive diffusion, reaching 264±24μg/cm(2)h (mean±SD). Based on these results, and taking into account the pharmacokinetics of almotriptan, therapeutic drug plasma levels for the management of migraine could be achieved via transdermal iontophoresis using a reasonably sized (around 7.2cm(2)) patch. PMID:21736929

  13. Ethosomes as delivery system for transdermal administration of vinpocetine.

    PubMed

    Mao, Yan-Ting; Hua, Hai-Ying; Zhang, Xiang-Guo; Zhu, Dong-Xue; Li, Feng; Gui, Zhen-Hua; Zhao, Yong-Xing

    2013-05-01

    The purpose of the present study was to develop a novel transdermal vinpocetine patch containing a stable formulation and with good entrapment efficiency, and percutaneous absorption which via ethosome. Ethosome was found to be a more efficient delivery carrier with high encapsulation capacities (79.5% +/- 1.8%) and nanometric size (180.7 +/- 1.5 nm). In vitro percutaneous permeation experiments demonstrated that the permeation of vinpocetine through abdominal skin of Sprague Dawley was significantly increased when ethosome was used. The vinpocetine transdermal fluxes from ethosome gel (3.56 +/- 0.13 microg/cm2/h) were 6.72 and 3.10 times higher than that of vinpocetine gel solution and vinpocetine aueous solution, respectively. Furthermore, the AUC(0 --> infinity), and eliminiation half-life by the transdermal administration were significantly higher than those by the intragastric administration (P < 0.01). The study demonstrated that ethosome is a promising vesicular carrier for enhancing percutaneous absorption of vinpocetine. PMID:23802438

  14. A Randomized, Double-Blind, Placebo-Controlled, Laboratory Classroom Assessment of Methylphenidate Transdermal System in Children with ADHD

    ERIC Educational Resources Information Center

    McGough, James J.; Wigal, Sharon B.; Abikoff, Howard; Turnbow, John M.; Posner, Kelly; Moon, Eliot

    2006-01-01

    Objective: This study evaluates the efficacy, duration of action, and tolerability of methylphenidate transdermal system (MTS) in children with ADHD. Method: Participants were dose optimized over 5 weeks utilizing patch doses of 10, 16, 20, and 27 mg applied in the morning and worn for 9 hours. Following optimization, 80 participants were…

  15. Sedation with etomidate-fentanyl versus propofol-fentanyl in colonoscopies: A prospective randomized study

    PubMed Central

    Banihashem, Nadia; Alijanpour, Ebrahim; Basirat, Majid; Shokri Shirvany, Javad; Kashifard, Mehrdad; Taheri, Hasan; Savadkohi, Shahriyar; Hosseini, Vahid; Solimanian, Seyed Sedigheh

    2015-01-01

    Background: The combination of propofol-fentanyl for sedation during colonoscopy is characterized by high prevalence of side effects. Etomidate-fentanyl provides fewer hemodynamic and respiratory complications. The aim of our study was to compare the safety and efficacy of propofol-fentanyl and etomidate-fentanyl for conscious sedation in elective colonoscopy. Methods: This double-blind clinical trial was conducted on 90 patients aged between 18- 55 years old who were candidates for elective colonoscopy. Patients were randomized to receive sedation with fentanyl plus propofol or etomidate. Two minutes after injecting 1 micro/kg of fentanyl, the patients received 0.5mg/kg propofol by infusion (25 µ/kg/min) or 0.1 mg/kg etmoidate (15 µ/kg/min). Pulse rate, mean arterial blood pressure, respiratory rate, and saturation of peripheral oxygen (SPO2) were monitored. In addition, the patient and colonoscopist satisfaction, the recovery time, sedation and pain score in both groups were assessed. Results: Sedation score in propofol group was higher. Pain score as well as the physician and patient satisfaction showed no significant difference between the two study groups. Hemodynamic changes and arterial saturation were the same in both groups. The duration of recovery was 1.27±0.82 minutes in the etomidate group; versus 2.57±2.46 minutes in the propofol group (P=0.001). Recovery time in the etmoid group was 2.68±3.14 minutes and in the propofol group was 5.53±4.67 minutes (p=0.001). Conclusion: The combination of fentanyl and etomidate provides an acceptable alternative to sedation with fentanyl and propofol with the advantage of significantly faster recovery time, in the outpatient setting. PMID:26221491

  16. Unique Scopolamine Withdrawal Syndrome After Standard Transdermal Use.

    PubMed

    Manno, Maurizio; Di Renzo, Gianfranco; Bianco, Pasquale; Sbordone, Carmine; De Matteis, Francesco

    2015-01-01

    We report the case of a 62-year-old woman who developed a withdrawal syndrome after using a standard 1.5-mg transdermal scopolamine (TDS) patch behind the ear to prevent motion sickness during sailing. The patient, who had used TDS occasionally for years without significant adverse effects, more recently, having worn a patch continuously for 7 days, approximately 24 to 36 hours after removing the patch developed dizziness, nausea, sweating, fatigue, and drowsiness. All symptoms disappeared without therapy in about 2 days. Approximately 1 year after the first episode, though, a very similar, more severe disabling reaction developed on 2 occasions. Drowsiness and malaise were accompanied by severe asthenia, orthostatic sweating, inability to stand, and hypotension. All clinical tests (electrocardiogram; spirometry; blood cell count; plasma levels of cortisol, sodium, and potassium; and liver and kidney function tests) were negative, and symptoms disappeared slowly, after several days. Although we are certain that scopolamine was responsible for the symptoms, we are less clear as to the nature of the disorder. The effects being more severe after a more prolonged use of the TDS patch, the increase in severity each successive time, and the time lag between removing the patch and appearance of symptoms all indicated a withdrawal syndrome for which several mechanisms may be suggested. PMID:26366965

  17. [Transdermal buprenorphine: a current overview of pharmacological and clinical data].

    PubMed

    Faymonville, M E; Libbrecht, D

    2008-11-01

    Our understanding of the pathophysiologic mechanisms of chronic pain progresses; the complexity of the problem justifies our need for new molecules and new ways of administration that will help to further optimise and better individualize our pharmacologic therapies. Whereas acute pain can be considered an alarm signal, chronic pain constitutes, per se, a syndrome that requires a meticulous selection of the analgesic drug(s). Since pain is permanent, the continuous administration of the analgesic is recommended rather than an on demand administration. Transdermic modes of administration are of value for the treatment of chronic pain because they allow a progressive delivery of the active compound together with the maintenance of stable plasma levels of the drug. Buprenorphine is a semi-synthetic opioid that is available in the sublingual, injectable, or transdermic forms. The matrix patch of buprenorphine represents a major asset for the treatment of chronic pain, whether it be cancerous in origin, or not. Its efficacy and safety have been clearly demonstrated in randomised double blind trials as well as in post-marketing surveillance observations. Buprenorphine, administered as a transdermal therapeutic system, induces a dose-related pain relief, whatever the nature of the pain and the age of the patient. Buprenorphine also exerts an analgesic action on neuropathic pain. It differs from other opioids by its affinity as a partial agonist on mu and kappa receptors, and as a complete agonist of ORL-1 receptors. Therefore, transdermal buprenorphine will be useful to all physicians having to control severe pain by powerful opioids. PMID:19112993

  18. Fentanyl supplementation of sevoflurane induction of anaesthesia.

    PubMed

    Plastow, S E; Hall, J E; Pugh, S C

    2000-05-01

    Sevoflurane induction of anasthesia has been examined extensively, but little is known about the usefulness of other drugs as adjuncts to hasten and smooth the process. Sixty patients, undergoing surgery of a type suitable for a spontaneous respiration, laryngeal mask airway anasthetic technique, were randomly allocated to receive 1.0 microgram.kg-1 intravenous fentanyl or the equivalent volume of normal saline, 30 s prior to triple-breath induction with sevoflurane. The study was double-blind. There were no differences between the groups for the times to loss of eyelash reflex, jaw relaxation, insertion of the laryngeal mask airway or regular settled breathing. However, there was a difference in the incidence of adverse airway events (breath-holding, coughing and laryngospasm) between the two groups (16.5% in the fentanyl group and 40% in the placebo group); this did not reach statistical significance. Both groups were haemodynamically stable throughout induction, although the fentanyl group had a statistically significant decrease in systolic blood pressure at 4 min compared with the placebo group, which was not considered clinically relevant. We conclude that fentanyl has no significant influence over the speed and quality of sevoflurane induction. PMID:10792142

  19. Epidural Analgesia With Bupivacaine and Fentanyl Versus Ropivacaine and Fentanyl for Pain Relief in Labor

    PubMed Central

    Guo, Shanbin; Li, Bo; Gao, Chengjie; Tian, Yue

    2015-01-01

    Abstract The aim of this study was to compare the efficacy and safety of the combinational use of bupivacaine and fentanyl versus ropivacaine and fentanyl in epidural analgesia for labor. Multiple electronic databases were searched by using appropriate MeSH terms, and keywords for original research papers published before October 2014. Meta-analyses were based on mean differences between the groups as well as odds ratios. Statistical heterogeneity was tested by I2 index. Fifteen randomized controlled trials, recruiting 2097 parturient mothers overall, were selected for the meta-analyses. Concentrations of the preparations used (weight/volume; mean and standard deviations) were bupivacaine 0.1023% ± 0.0375%, ropivacaine 0.1095% ± 0.042%, and fentanyl 0.00021% ± 0.000089%. There were no statistically significant differences between both the combinations in the mean change in Visual Analog Score for pain during labor, incidence of instrumental or cesarean delivery, neonate Apgar score of <7, maternal satisfaction, duration of either first or second stage of labor, oxytocin use for induction, onset of analgesia, and duration of analgesia. Women who received ropivacaine and fentanyl had significantly lower incidence of motor blocks (odds ratio [95% CI] = 0.38 [0.30, 0.48] P < 0.00001, fixed effect and 0.38 [0.27, 0.54] P < 0.0001, random effects I2 30%) when compared with women who received bupivacaine and fentanyl. Incidence of side effects was similar for both the combinations. Analgesia with ropivacaine in combination with fentanyl at 0.1%:0.0002% ratio for labor pain relief is associated with lower incidence of motor blocks in comparison with analgesia with bupivacaine and fentanyl at similar ratio (0.1%: 0.0002%). PMID:26061307

  20. Transdermal delivery of naloxone: skin permeation, pharmacokinetic, irritancy and stability studies.

    PubMed

    Panchagnula, Ramesh; Bokalial, Ranadeep; Sharma, Puneet; Khandavilli, Sateesh

    2005-04-11

    The current investigation aims to evaluate ex vivo, in vivo performance, stability and irritancy potential of a transdermal formulation of naloxone (NLX) developed at our laboratory at different concentrations (10, 20 and 30mg/g of gel) in a transdermal reservoir patch. Ex vivo permeation studies were performed by employing porcine and rat skins. In vivo performance was assessed in Sprague-Dawley rats by single and multiple application of the patch. Further stability of the formulation was established for 3 months at accelerated stability conditions as per ICH guidelines. Amongst the barriers used the rat skin was found to be more permeable than the porcine epidermis and the flux across each barrier increased with increasing thermodynamic activity of drug in the gel. Based on ex vivo data, the surface area (SA) of the patch was predicted to be 39.6 cm(2) in order to achieve therapeutic blood levels. Upon single dose administration, the steady-state levels were maintained from 4-48 h, which proves the clear advantage of transdermal delivery system over the current mode of administration, i.e., intravenous (i.v.) bolus which is effective upto a maximum of 1.5h. Upon multiple dose administration, the sustained steady state for 12h, even after patch removal proves the formation of drug depot in the skin. The formulations were found to be stable with respect to NLX assay and penetration enhancer efficacy upto 3 months under accelerated stability conditions. The alteration of penetration barrier function, as evidenced by increased trans epidermal water loss (TEWL) was not accompanied by any significant amount of skin irritation measured using laser doppler velocimetry (LDV). The developed transdermal delivery system of NLX is efficacious, stable and safe upon single and multiple dose applications each lasting for 48 h. PMID:15778059

  1. Transdermal nicotine alters some of marihuana's effects in male and female volunteers.

    PubMed

    Penetar, David M; Kouri, Elena M; Gross, Michelle M; McCarthy, Elissa M; Rhee, Christina K; Peters, Erica N; Lukas, Scott E

    2005-08-01

    Despite the fact that tobacco and marihuana are often used together, relatively little is known about the effects of this combination. In order to investigate the effects of the principal psychoactive component in tobacco smoke, nicotine, on marihuana-induced intoxication, we conducted a double blind, cross-over experiment using nicotine transdermal patches. Ten male and 10 female participants received either placebo or a 21 mg transdermal nicotine patch 4 h before smoking one of two marihuana cigarettes (1.99 or 3.51% delta-9-tetrahydrocannabinol (Delta(9) THC) content). Measurements of physiological activity (heart rate, blood pressure, and skin temperature) and subjective effects (self-reports of drug effects on visual analog scales (VAS) and the Addiction Research Center Inventory (ARCI)) were made periodically before and for 3h after smoking. Nicotine pre-treatment enhanced several responses to marihuana, in particular, heart rate, reports of "stimulated" on the visual analog scales, and scores on the Amphetamine scale of the ARCI. Male participants reported a more pronounced effect of marihuana that persisted longer than that of the female participants. Compared to the male participants, female participants experienced an attenuated response to marihuana and were less affected by the drug combination. The results of this study show that nicotine can have an important influence on the subjective and physiological effects of smoked marihuana. These effects have implications for the safety and efficacy of marihuana smokers who are self-medicating with the nicotine transdermal patch to manage their tobacco dependence. PMID:16002030

  2. Cabbage Patch

    NASA Technical Reports Server (NTRS)

    1997-01-01

    This Sojourner rover image of the Cabbage Patch shows small rounded objects on the surface that are about 3-4 cm across. Some of these are within excavations, which are about 0.5 cm wide. Several questions arise about the pebbles: Why are they rounded? Where did they come from? What do they mean?

    Geologists use MULTIPLE WORKING HYPOTHESES when attempting to explain observations. Some hypotheses that could account for the pebbles are: They were rounded during transport by waters of catastrophic floods and deposited on the Ares Vallis floodplain They were rounded by wave action on an ancient Martian beach They were rounded during glacial transport They are glasses that were produced by melting during impact cratering. The glass was first ejected from the crater, then molded into spherical shapes or drops as it traveled through the atmosphere, and finally was deposited at the sites They are spatter from lava flows They are nodules brought up from the deep Martian interior by lava flows or pyroclastic eruptions. They are concretions formed in sedimentary rocks They came from ancient conglomerate rocks. The pebbles were rounded by water action and subsequently lithified into conglomerate rocks. Later, the waters of catastrophic floods transported the conglomerates and deposited them on the Ares floodplain. The pebbles were then freed from the rocks by weathering. A combination of the above

    Mars Pathfinder is the second in NASA's Discovery program of low-cost spacecraft with highly focused science goals. The Jet Propulsion Laboratory, Pasadena, CA, developed and manages the Mars Pathfinder mission for NASA's Office of Space Science, Washington, D.C. JPL is a division of the California Institute of Technology (Caltech).

  3. Dexmedetomidine-fentanyl versus propofol-fentanyl in flexible bronchoscopy: A randomized study

    PubMed Central

    YUAN, FENG; FU, HONGGUANG; YANG, PENGJU; SUN, KAI; WU, SHUBIAO; LV, MIAOMIAO; DONG, ZHENZHEN; DONG, TIELI

    2016-01-01

    The aim of the present study was to evaluate the effect of a combination of dexmedetomidine and fentanyl on peripheral oxygen saturation (SpO2) and hemodynamic stability in patients undergoing flexible bronchoscopy. One hundred patients undergoing elective flexible bronchoscopy were randomized into either a propofol-fentanyl group (PF group; n=50) or a dexmedetomidine-fentanyl group (DF group; n=50). SpO2 values, heart rate (HR), systolic and diastolic blood pressure (SBP and DBP), patients' cough scores and discomfort scores as determined by patients and bronchoscopists, levels of sedation, number of times that additional lidocaine was required, elapsed time until recovery, and adverse events were recorded. The mean SpO2 values in the DF group were significantly higher than those in the PF group (P<0.01), and HR, SBP and DBP were significantly lower in the DF group than in the PF group (P<0.05). There were no statistically significant differences between the two groups in terms of cough scores or discomfort scores, sedation levels, or number of times that additional lidocaine was required (P>0.05). Elapsed time until recovery in the DF group was significantly longer than in the PF group (P=0.002). The incidence of hypoxemia was significantly lower in the DF group than in the PF group (P=0.027), but the incidence of bradycardia was significantly higher in the DF group than in the PF group (P=0.037). Dexmedetomidine-fentanyl was superior to propofol-fentanyl in providing satisfactory SpO2. Furthermore, dexmedetomidine-fentanyl attenuated hemodynamic responses during bronchoscopy and maintained hemodynamic stability in the early stage of the procedure. PMID:27347086

  4. The iontophoretic transdermal system formulation of sumatriptan as a new option in the acute treatment of migraine: a perspective.

    PubMed

    Vikelis, Michail; Spingos, Konstantinos C; Rapoport, Alan M

    2015-07-01

    An iontophoretic transdermal system (ITS) (skin patch) formulation of sumatriptan for the acute treatment of migraine attacks was approved by the US Food and Drug Administration in January 2013. This transdermal system bypasses the gastrointestinal tract, as it uses low electrical current to move sumatriptan transdermally into the subcutaneous tissue. Randomized, double-blind, controlled clinical trials have demonstrated minimal triptan-related side effects and superior efficacy versus placebo, comparable with other sumatriptan formulations. Sumatriptan ITS can be applied successfully during a mild or severe migraine attack. According to pharmacokinetic properties and clinical data, sumatriptan ITS may be a good choice for people with migraine and severe nausea, vomiting or gastroparesis, those with intolerable triptan-related adverse events and those not responding optimally to oral medications. PMID:26136843

  5. The iontophoretic transdermal system formulation of sumatriptan as a new option in the acute treatment of migraine: a perspective

    PubMed Central

    Spingos, Konstantinos C.; Rapoport, Alan M.

    2015-01-01

    An iontophoretic transdermal system (ITS) (skin patch) formulation of sumatriptan for the acute treatment of migraine attacks was approved by the US Food and Drug Administration in January 2013. This transdermal system bypasses the gastrointestinal tract, as it uses low electrical current to move sumatriptan transdermally into the subcutaneous tissue. Randomized, double-blind, controlled clinical trials have demonstrated minimal triptan-related side effects and superior efficacy versus placebo, comparable with other sumatriptan formulations. Sumatriptan ITS can be applied successfully during a mild or severe migraine attack. According to pharmacokinetic properties and clinical data, sumatriptan ITS may be a good choice for people with migraine and severe nausea, vomiting or gastroparesis, those with intolerable triptan-related adverse events and those not responding optimally to oral medications. PMID:26136843

  6. Reduction of Aggressive Episodes After Repeated Transdermal Nicotine Administration in a Hospitalized Adolescent with Autism Spectrum Disorder

    PubMed Central

    Lewis, Alan S.; Qayyum, Zheala; Koslosky, Kourtney; Picciotto, Marina R.; Volkmar, Fred R.

    2016-01-01

    Aggression remains a major cause of morbidity in patients with autism spectrum disorder (ASD). Current pharmacotherapy for aggression is not always effective and is often associated with morbidity. Nicotinic acetylcholinergic neurotransmission may play a prominent role in ASD pathophysiology based on human and animal studies, and preclinical studies show nicotine administration can reduce aggression-related behaviors. Transdermal nicotine has been used to treat agitation in neuropsychiatric conditions with cholinergic dysfunction. Here we report the use of transdermal nicotine as an adjunctive medication to treat aggression in a hospitalized adolescent with ASD. Nicotine patch was recurrently well tolerated, and reduced the need for emergency medication and restraint. These findings suggest further study of transdermal nicotine for aggression comorbid with ASD is warranted. PMID:25982311

  7. Clinical pharmacology of fentanyl in preterm infants. A review.

    PubMed

    Pacifici, Gian Maria

    2015-06-01

    Fentanyl is a synthetic opioid that is very important in anesthetic practice because of its relatively short time to peak analgesic effect and the rapid termination of action after small bolus doses. The objective of this survey is to review the clinical pharmacology of fentanyl in preterm infants. The bibliographic search was performed using PubMed and EMBASE databases as search engines. In addition, the books Neofax: A manual of drugs used in neonatal care and Neonatal formulary were consulted. Fentanyl is N-dealkylated by CYP3A4 into the inactive norfentanyl. Fentanyl may be administered as bolus doses or as a continuous infusion. In neonates, there is a remarkable interindividual variability in the kinetic parameters. In neonates, fentanyl half-life ranges from 317 minutes to 1266 minutes and in adults it is 222 minutes. Respiratory depression occurs when fentanyl doses are >5 μg/kg. Chest wall rigidity may occur in neonates and occasionally is associated with laryngospasm. Tolerance to fentanyl may develop after prolonged use of this drug. Significant withdrawal symptoms have been reported in infants treated with continuous infusion for 5 days or longer. Fentanyl is an extremely potent analgesic and is the opioid analgesic most frequently used in the neonatal intensive care unit. PMID:25176283

  8. Current developments using emerging transdermal technologies in physical enhancement methods.

    PubMed

    Nanda, A; Nanda, S; Ghilzai, N M Khan

    2006-07-01

    Transdermal drug delivery using patches offers many advantages, but is limited primarily by the stratum corneum barrier. Amongst the various methods to overcome this barrier, physical methods are gaining in popularity and commercial devices development. Macroflux, MTS and Silex are based on microporation, involving use of microneedles that pierce thereby bypassing the stratum corneum. Intraject , Powderject and Helios are based on needleless jet injectors wherein very fine, solid particulate drug, is fired directly into the skin, using high-pressure gas. Med- Tats incorporate use of modified drug-containing tattoos, which bind to the skin, wherein the drug is absorbed. CHADD is based on use of heat, which increases skin - permeation of drugs. High-power, pulsed lasers transmit positive mechanical forces to the skin and create intercellular channels into the skin transiently. Sonophoresis involves use of ultrasound, which transiently disrupts the stratum corneum barrier. This technique offers a non-invasive transdermal extraction of interstitial fluids of sampling body fluids. Modified Liposomes include Ethosomes (containing alcohol) and Transferosomes (containing surfactants), which have enhanced skin permeability. Pulsed magnetic fields may create transient pores in cell membranes, including skin, resulting in increased permeation. Iontophoresis is based on application of electric potential for enhancing the movement of substances to and from the body. Dupel, Ionzyme, Liposite, ETrans, Phoresor and Drionic are based on iontophoresis. GlucoWatch offers non-invasive blood glucose monitoring, based on reverse iontophoresis. This review outlines recent commercial developments in physical transdermal drug delivery technology and the specific devices and applications being targeted by the pharmaceutical industry. PMID:16848725

  9. Nanosized ethosomes bearing ketoprofen for improved transdermal delivery.

    PubMed

    Chourasia, Manish K; Kang, Lifeng; Chan, Sui Yung

    2011-05-01

    The potential of ethosomes for delivering ketoprofen via skin was evaluated. The ethosomes were prepared, optimized and characterized. Vesicular shape, size and entrapment efficiency were determined by transmission electron microscopy, dynamic light scattering and minicolumn centrifugation technique, respectively. Vesicle sizes varied from 120.3±6.1 to 410.2±21.8 nm depending on the concentrations of soya phosphatidyl choline (SPC) and ethanol. Entrapment efficiency increased with concentrations of SPC and ethanol. The formulations exhibited entrapment efficiencies of 42-78%. In vitro release through cellophane membrane showed sustained release of drug from ethosomal formulations in contrast to hydroalcoholic drug solution (HA), which released most of the drug within 2-3 h. In vitro drug permeation across human skin revealed improved drug permeation and higher transdermal flux with ethosomal formulations compared to hydroethanolic drug solution. Kinetics of in vitro skin permeation showed zero order drug release from formulations. Based on in vitro transdermal flux, the estimated steady state in vivo plasma concentration from ethosomes attained therapeutic drug levels whereas hydroalcoholic drug solution exhibited sub therapeutic drug concentration with a patch size of 50 cm(2). Skin permeation of ethosomal formulations assessed by confocal microscopy revealed enhanced permeation of Rhodamine 123 loaded formulation in comparison to the hydroalcoholic solution. PMID:25755983

  10. Starch nanocrystals based hydrogel: Construction, characterizations and transdermal application.

    PubMed

    Bakrudeen, Haja Bava; Sudarvizhi, C; Reddy, B S R

    2016-11-01

    Bio-based nanocomposites were prepared using starch nanocrystals obtained by acid hydrolysis of native starches using different acid sources. In recent times, focuses on starch nanocrystals (SNCs) have been increasing in number of research works dedicated to the development of bio-nanocomposites by blending with different biopolymeric matrices. The work mainly deals with the preparation of starch nanocrystals using different native starches by acid hydrolysis using hydrochloric acid and trifluroacetic acid. The as-prepared starch nanocrystals are having high crystallinity and more platelet morphologies, and used as a drug carrying filler material in the hydrogel formulations with the care of different polymer matrices. The condensed work also concentrates on the dispersion of antiviral drug in the hydrogels, which are applied onto biocompatible bio-membrane to be formulating a complete transdermal patch. The acid hydrolysed starch nanocrystals were thoroughly characterized using TEM, SEM, particle size analysis and zeta potential. Their thermal stability and the crystalline properties were also characterized using TG-DSC and XRD respectively. The physiochemical interaction and compatibility between the drug and the SNCs filler in the polymeric hydrogels were evaluated using FT-IR analysis. The formulated hydrogels were subjected to evaluation of in vitro permeation studies using Franz diffusion studies. The in vitro study was indicated substantial guarantee for the fabrication of drug dispersed in polymeric hydrogels using SNCs as filler matrices for a successful transdermal drug delivery. PMID:27524091

  11. Nanosized ethosomes bearing ketoprofen for improved transdermal delivery

    PubMed Central

    Chourasia, Manish K.; Kang, Lifeng; Chan, Sui Yung

    2011-01-01

    The potential of ethosomes for delivering ketoprofen via skin was evaluated. The ethosomes were prepared, optimized and characterized. Vesicular shape, size and entrapment efficiency were determined by transmission electron microscopy, dynamic light scattering and minicolumn centrifugation technique, respectively. Vesicle sizes varied from 120.3±6.1 to 410.2±21.8 nm depending on the concentrations of soya phosphatidyl choline (SPC) and ethanol. Entrapment efficiency increased with concentrations of SPC and ethanol. The formulations exhibited entrapment efficiencies of 42–78%. In vitro release through cellophane membrane showed sustained release of drug from ethosomal formulations in contrast to hydroalcoholic drug solution (HA), which released most of the drug within 2–3 h. In vitro drug permeation across human skin revealed improved drug permeation and higher transdermal flux with ethosomal formulations compared to hydroethanolic drug solution. Kinetics of in vitro skin permeation showed zero order drug release from formulations. Based on in vitro transdermal flux, the estimated steady state in vivo plasma concentration from ethosomes attained therapeutic drug levels whereas hydroalcoholic drug solution exhibited sub therapeutic drug concentration with a patch size of 50 cm2. Skin permeation of ethosomal formulations assessed by confocal microscopy revealed enhanced permeation of Rhodamine 123 loaded formulation in comparison to the hydroalcoholic solution. PMID:25755983

  12. Improvement in bioavailability of transdermally applied flurbiprofen using tulsi (Ocimum sanctum) and turpentine oil.

    PubMed

    Charoo, Naseem Ahmad; Shamsher, Areeg Anwer Ali; Kohli, Kanchan; Pillai, Krishna; Rahman, Ziyaur

    2008-09-01

    Penetration enhancing potential of tulsi and turpentine oil on transdermal delivery of flurbiprofen, a potent non-steroidal anti-inflammatory agent, was investigated. The transdermal permeation rate of flurbiprofen across the rat abdominal skin from binary solvent mixture composition of propylene glycol (PG):isopropyl alcohol (IPA) (30:70%, v/v) was 98.88 microg/cm(2)/h, significantly higher than other binary solvent mixtures. The corresponding steady state plasma concentration, 0.71 microg/ml, was much lower than required steady state plasma concentration of 3-5 microg/ml. Hence influence of tulsi and turpentine oil in the optimized binary solvent mixture along with the increased drug load on the flurbiprofen permeation was evaluated. The magnitude of the flux enhancement factor with turpentine oil and tulsi oil was 2.4 and 2.0 respectively at 5% (v/v) concentration beyond which there was no significant increase in the flux. Addition of 2% (w/v) hydroxypropyl methylcellulose (HPMC), as a thickening agent, resulted in desired consistency for the fabrication of patch with insignificant effect on permeation rate of flurbiprofen. The reservoir type of transdermal patch formulation, fabricated by encapsulating the flurbiprofen reservoir solution within a shallow compartment moulded from polyester backing film and microporous ethyl vinyl acetate membrane, did not modulate the skin permeation of flurbiprofen through rat skin in case of turpentine formulations whereas flux of formulations with tulsi oil was significantly altered. The influence of penetration enhancer and solvents on the anatomical structure of the rat skin was studied. Enhancement properties exhibited by turpentine oil and tulsi oil in optimized binary solvent mixture were superior as compared to solvent treated and normal control groups with negligible skin irritation. The fabricated transdermal patches were found to be stable. The bioavailability of flurbiprofen with reference to orally administered

  13. Intra-articular drug delivery from an optimized topical patch containing teriflunomide and lornoxicam for rheumatoid arthritis treatment: does the topical patch really enhance a local treatment?

    PubMed

    Xi, Honglei; Cun, Dongmei; Xiang, Rongwu; Guan, Yanli; Zhang, Yuxiu; Li, Yuanru; Fang, Liang

    2013-07-10

    Patients with rheumatoid arthritis (RA) often bear joint destruction and symptomatic pain. The aim of this work is to develop a compound transdermal patch containing teriflunomide (TEF) and lornoxicam (LOX) to transport these drugs across the skin with the isochronous permeation rates for RA therapy and investigate intra-articular delivery of TEF and LOX following transdermal patches applied topically. The salts of TEF and LOX with organic amines diethylamine (DEtA), triethylamine (TEtA), diethanolamine (DEA), triethanolamine (TEA) and N-(2'-hydroxy-ethanol)-piperdine (NP) were prepared to improve the skin permeation of the parent drug. The optimized patch formulation is obtained from a 3-factor, 2-level central composite design. After topical application of the optimized compound patch to only one knee joint in rabbit, intra-articular delivery of TEF and LOX on the application site was compared with that on the non-application site. Anti-inflammatory and analgesic effects of the optimized compound patch were evaluated using the adjuvant arthritis model and the pain model induced by acetic acid, respectively. The in vitro experiment results showed that the amine salts of TEF and LOX, especially TEF-TEtA and LOX-TEtA, enhanced the skin permeation of TEF and LOX from the transdermal patch system. The optimal formulation successfully displayed isochronous permeation rates for TEF and LOX across rabbit skin, and was defined with 5% of TEF-TEtA, 10% of LOX-TEtA and 15% of azone. The in vivo study showed that TEF and LOX from transdermal patches were transferred into skin, ligament and fat pad on the application site by direct diffusion and on the non-application site by the redistribution of systemic blood supply, while local absorption of TEF and LOX in synovial fluid originated from the systemic blood supply rather than direct diffusion. In the RA rat model, the results of swelling inhibition on primary arthritis of bilateral hind paws further confirmed the above

  14. Human Growth Hormone Delivery with a Microneedle Transdermal System: Preclinical Formulation, Stability, Delivery and PK of Therapeutically Relevant Doses

    PubMed Central

    Ameri, Mahmoud; Kadkhodayan, Miryam; Nguyen, Joe; Bravo, Joseph A.; Su, Rebeca; Chan, Kenneth; Samiee, Ahmad; Daddona, Peter E.

    2014-01-01

    This study evaluated the feasibility of coating formulated recombinant human growth hormone (rhGH) on a titanium microneedle transdermal delivery system, Zosano Pharma (ZP)-hGH, and assessed preclinical patch delivery performance. Formulation rheology and surface activity were assessed by viscometry and contact angle measurement. rhGH liquid formulation was coated onto titanium microneedles by dip-coating and drying. The stability of coated rhGH was determined by size exclusion chromatography-high performance liquid chromatography (SEC-HPLC). Preclinical delivery and pharmacokinetic studies were conducted in female hairless guinea pigs (HGP) using rhGH coated microneedle patches at 0.5 and 1 mg doses and compared to Norditropin® a commercially approved rhGH subcutaneous injection. Studies demonstrated successful rhGH formulation development and coating on microneedle arrays. The ZP-hGH patches remained stable at 40 °C for six months with no significant change in % aggregates. Pharmacokinetic studies showed that the rhGH-coated microneedle patches, delivered with high efficiency and the doses delivered indicated linearity with average Tmax of 30 min. The absolute bioavailability of the microneedle rhGH patches was similar to subcutaneous Norditropin® injections. These results suggest that ZP-transdermal microneedle patch delivery of rhGH is feasible and may offer an effective and patient-friendly alternative to currently marketed rhGH injectables. PMID:24838219

  15. Fentanyl Buccal Soluble Film: A Review in Breakthrough Cancer Pain.

    PubMed

    Garnock-Jones, Karly P

    2016-05-01

    Fentanyl buccal soluble film (Onsolis(®), Breakyl(®), Painkyl™) comprises two layers: a mucoadhesive layer containing the active drug, and an inactive layer with the aim of preventing the diffusion of fentanyl into the oral cavity. It is approved in several countries worldwide, including the USA and those of the EU, for the management of breakthrough cancer pain in opioid-tolerant, adult patients with cancer. This article reviews the pharmacological properties of fentanyl buccal soluble film and its clinical efficacy and tolerability in these patients. Fentanyl buccal soluble film provides an additional option for transmucosal delivery of fentanyl, with approximately half of the dose undergoing an initial, rapid absorption via the buccal mucosa (accounting for its high bioavailability). In clinical trials, fentanyl buccal soluble film was associated with significant improvements in pain intensity scores versus placebo and was generally well tolerated. The most common adverse events were typical opioid-associated adverse events, such as nausea and vomiting. Fentanyl buccal soluble film is a useful option for the treatment of breakthrough cancer pain in opioid-tolerant patients. PMID:27007271

  16. Brain injury and development in preterm infants exposed to fentanyl

    PubMed Central

    McPherson, Christopher; Haslam, Matthew; Pineda, Roberta; Rogers, Cynthia; Neil, Jeffrey J.; Inder, Terrie E.

    2015-01-01

    Background Fentanyl is commonly utilized in preterm infants. Relatively little is known regarding the neurodevelopmental outcomes of preterm infants exposed to fentanyl. Objective To investigate the association between cumulative fentanyl dose and brain injury and diameters in a cohort of preterm infants Methods Data on demographics, perinatal course, and neonatal course, including total fentanyl exposure prior to term equivalent age, were retrospectively evaluated for 103 infants born at ≤ 30 weeks gestational age who underwent magnetic resonance imaging at term equivalent age (mean gestational age 26.9 ± 1.8 weeks). Magnetic resonance images were evaluated for brain injury and regional brain diameters. Developmental testing was conducted at term equivalent and 2 years of age. Results Seventy-eight infants (76%) received fentanyl (median cumulative dose 3 μg/kg, interquartile range 1 – 441 μg/kg). Cumulative fentanyl dose in the first week of life correlated with the incidence of cerebellar hemorrhage after correction for covariates (OR 2.1, 95% confidence interval 1.1 – 4.1). Cumulative fentanyl dose before term equivalent age correlated with reductions in transverse cerebellar diameter after correction for covariates including the presence of cerebellar hemorrhage (r = 0.461, p = 0.002). No correlation was detected between cumulative fentanyl dose and development at 2 years of age. Conclusions Higher cumulative fentanyl dose in preterm infants correlated with a higher incidence of cerebellar injury and lower cerebellar diameter at term equivalent age. Our findings must be taken with caution, but emphasize the need for future prospective trials examining the risks and benefits of commonly utilized analgesic agents in preterm infants. PMID:26369570

  17. Bacterial cellulose membranes as transdermal delivery systems for diclofenac: in vitro dissolution and permeation studies.

    PubMed

    Silva, Nuno H C S; Rodrigues, Artur Filipe; Almeida, Isabel F; Costa, Paulo C; Rosado, Catarina; Neto, Carlos Pascoal; Silvestre, Armando J D; Freire, Carmen S R

    2014-06-15

    Bacterial cellulose (BC) membranes were explored as novel nanostructured transdermal delivery systems for diclofenac sodium salt (a typical non-steroidal anti-inflammatory drug). Diclofenac sodium salt loaded BC membranes were prepared through a simple methodology, using glycerol as plasticizer, and characterized in terms of structure, morphology and swelling behavior. The membranes were very homogeneous, quite flexible and presented a considerably higher swelling behavior when compared with pure BC. In vitro diffusion studies with Franz cells, were conducted using human epidermal membranes, and showed that the incorporation of diclofenac in BC membranes provided similar permeation rates to those obtained with commercial patches and substantially lower than those observed with a commercial gel. This release profile together with the ease of application and the simple preparation and assembly of the drug-loaded membranes clearly indicates the enormous potentialities of using BC membranes for transdermal administration of diclofenac. PMID:24721077

  18. Transdermal rotigotine for the perioperative management of restless legs syndrome

    PubMed Central

    2012-01-01

    Background Immobilisation, blood loss, sleep deficiency, and (concomitant) medications during perioperative periods might lead to acute exacerbation of symptoms in patients with the restless legs syndrome (RLS). Continuous transdermal delivery of the dopamine agonist rotigotine provides stable plasma levels over 24 h and may provide RLS patients with a feasible treatment option for perioperative situations. To assess the feasibility of use of rotigotine transdermal patch for the perioperative management of moderate to severe RLS, long-term data of an open-label extension of a rotigotine dose-finding study were retrospectively reviewed. Methods The data of all 295 patients who had entered the 5-year study were screened independently by two reviewers for the occurrence of surgical interventions during the study period. The following data were included in this post-hoc analysis: patient age, sex, surgical intervention and outcome, duration of hospital stay, rotigotine maintenance dose at the time of surgery, rotigotine dose adjustment, and continuation/discontinuation of rotigotine treatment. All parameters were analysed descriptively. No pre-specified efficacy assessments (e.g. IRLS scores) were available for the perioperative period. Results During the study period, 61 surgical interventions were reported for 52 patients (median age, 63 years; 67% female); the majority of patients (85%) had one surgical intervention. The mean rotigotine maintenance dose at time of surgery was 3.1 ± 1.1 mg/24 h. For most interventions (95%), rotigotine dosing regimens were maintained during the perioperative period. Administration was temporarily suspended in one patient and permanently discontinued in another two. The majority (96%) of the patients undergoing surgery remained in the study following the perioperative period and 30 of these patients (61%) completed the 5-year study. Conclusions Although the data were obtained from a study which was not designed to assess

  19. Serotonin syndrome precipitated by fentanyl during procedural sedation.

    PubMed

    Kirschner, Ron; Donovan, J Ward

    2010-05-01

    Fentanyl is frequently used for analgesia during emergency procedures. We present the cases of 2 patients who developed agitation and delirium after intravenous fentanyl administration. These patients were chronically taking selective serotonin reuptake inhibitors (SSRIs). Both developed neuromuscular examinations consistent with serotonin syndrome, a diagnosis that must be established on the basis of clinical criteria. Although they required aggressive supportive care, including mechanical ventilation, both patients made a full recovery. Use of fentanyl for procedural sedation may precipitate serotonin syndrome in patients taking SSRIs or other serotonergic drugs. PMID:18757161

  20. Metal Patch Antenna

    NASA Technical Reports Server (NTRS)

    Chamberlain, Neil F. (Inventor); Hodges, Richard E. (Inventor); Zawadzki, Mark S. (Inventor)

    2012-01-01

    Disclosed herein is a patch antenna comprises a planar conductive patch attached to a ground plane by a support member, and a probe connector in electrical communication with the conductive patch arranged to conduct electromagnetic energy to or from the conductive patch, wherein the conductive patch is disposed essentially parallel to the ground plane and is separated from the ground plane by a spacing distance; wherein the support member comprises a plurality of sides disposed about a central axis oriented perpendicular to the conductive patch and the ground plane; wherein the conductive patch is solely supported above the ground plane by the support member; and wherein the support member provides electrical communication between the planer conductive patch and the ground plane.

  1. Lack of rebound during intermittent transdermal treatment with glyceryl trinitrate in patients with stable angina on background beta blocker.

    PubMed Central

    Holdright, D R; Katz, R J; Wright, C A; Sparrow, J L; Sullivan, A K; Cunningham, A D; Fox, K M

    1993-01-01

    OBJECTIVE--To assess whether intermittent transdermal treatment with glyceryl trinitrate causes clinically significant rebound in patients maintained on beta blockers for stable angina pectoris. DESIGN--Serial treadmill exercise testing in a double blind, randomised, placebo controlled cross over trial. Baseline exercise testing was performed at 0900 and 1100 at visit 1. Transdermal glyceryl trinitrate patches releasing 15 mg/24 h were applied at 2200 the evening before visits 2 and 3, and exercise testing was performed at 0900 the next morning. The patch was removed and replaced with either an identical patch or matching placebo and exercise tests were repeated two hours later. The alternative treatment was given at visit 3. SETTING--Tertiary referral centre. PATIENTS--14 patients with stable angina pectoris maintained on beta blocker treatment alone. MAIN OUTCOME MEASURES--Time to angina, 1 mm ST segment depression, and total time, together with heart rate, systolic blood pressure, and rate-pressure product. RESULTS--Active treatment improved treadmill performance at 0900 and 1100. Time to angina, time to 1 mm ST segment depression, and total time fell significantly on placebo compared with the 0900 exercise test on active treatment, but were not significantly different to the baseline exercise test either. CONCLUSIONS--Intermittent transdermal treatment with glyceryl trinitrate is not associated with the rebound phenomenon in patients maintained on beta blockers for stable angina pectoris. PMID:8096389

  2. Evaluation of microparticulate ovarian cancer vaccine via transdermal route of delivery.

    PubMed

    Tawde, Suprita A; Chablani, Lipika; Akalkotkar, Archana; D'Souza, Martin J

    2016-08-10

    Ovarian cancer is the fifth most commonly occurring malignancy in women, with the highest mortality rate among all the gynecological tumors. Microparticulate vaccine can serve as an immunotherapeutic approach with a promising antigenic delivery system without a need for conventional adjuvants. In this study, a microparticulate vaccine using whole cell lysate of a murine ovarian cancer cell line, ID8 was prepared by spray drying. Further, the effect of interleukins (ILs) such as IL-2 and IL-12 was evaluated in a separate study group by administering them with vaccine particles to enhance the immune response. The vaccine microparticles were administered to C57BL/6 female mice via transdermal alone and in combination with the oral route. The transdermal vaccine was delivered using a metallic microneedle device, AdminPen™. Orally administered microparticles also included an M-cell targeting ligand, Aleuria aurantia lectin, to enhance the targeted uptake from microfold cells (M-cells) in Peyer's patches of small intestine. In case of combination of routes, mice were given 5 transdermal doses and 5 oral doses administered alternatively, beginning with transdermal dose. At the end of vaccination, mice were challenged with live tumor cells. Vaccine alone resulted in around 1.5 times tumor suppression in case of transdermal and combination of routes at the end of 15th week when compared to controls. Inclusion of interleukins resulted in 3 times tumor suppression when administered with transdermal vaccine and around 9 times tumor suppression for the combination route of delivery in comparison to controls. These results were further potentiated by serum IgG, IgG1 and IgG2a titers. Moreover, CD8+ T-cell, CD4+ T-cell and NK (natural killer) cell populations in splenocytes were elevated in case of vaccinated mice. Thus, vaccine microparticles could trigger humoral as well as cellular immune response when administered transdermally and via combination of route of delivery

  3. Electret enhances transdermal drug permeation.

    PubMed

    Narasimha Sathyanarayana Murthy, Narasimha Sathyanarayana; Boguda, Vishwanath Anantharamaiah; Payasada, Kotrappa

    2008-01-01

    Electrets are polymeric discs that carry semi permanent electrostatic charge. These provide electrostatic potentials in the range of 500 to 3,000 V. In the current work, the effect of electret exposure on the skin permeability was investigated. Transdermal transport studies were carried out across porcine epidermis in Franz diffusion cells. Salicylic acid, fluorescein labeled dextrans (FD) and propofol were used as test diffusants. The ability of electret to enhance the transdermal permeation of salicylic acid was studied in vivo in Sprague Dawley rats. Electret enhanced the permeability of porcine epidermis to salicylic acid. The enhancement factor increased with the surface voltage, however it was independent of the nature of charge (+ or -). The enhancement by electret was cut-off at 1 kDa, as interpreted by studying the transport of FD. The electrets decreased the permeability of skin to propofol, a lipophilic diffusant. Pretreatment of porcine epidermis enhanced the iontophoretic transport of salicylic acid, whereas the same did not enhance the transport of salicylic acid by electroporation. It is most likely that electret exposure renders the lipid domains of stratum corneum more permeable to polar molecules and in turn hampers the diffusion of nonpolar diffusant. PMID:18175950

  4. Optimised transdermal delivery of pravastatin.

    PubMed

    Burger, Cornel; Gerber, Minja; du Preez, Jan L; du Plessis, Jeanetta

    2015-12-30

    Wiechers' programme "Formulating for Efficacy" initiated a new strategy to optimise the oil phase of topical formulations in order to achieve optimal transdermal drug delivery. This new approach uses the "Delivery Gap Theory" on any active pharmaceutical ingredients (APIs) to test if it could enhance transdermal drug delivery. The aim of the study was to formulate six different semi-solid formulations (three creams and three emulgels) with 2% pravastatin as the API in order to investigate the "Delivery Gap Principle", by determining which formulation would deliver pravastatin best to the target-site (system circulation). The three cream- and three emulgel formulations had different polarities, i.e. a formulation with polarity equal to that of the stratum corneum (optimised), a non-polar (lipophilic)- and a polar (hydrophilic)-formulation. Franz cell diffusion studies were executed over 12h and the optimised emulgel (2.578μg/cm(2)) had the highest median amount per area obtained. Tape stripping followed the diffusion studies and in the stratum corneum-epidermis, the hydrophilic emulgel (1.448μg/ml) contained the highest median pravastatin concentration and the epidermis-dermis the optimised emulgel (0.849μg/ml) depicted the highest pravastatin concentration. During this study, it was observed that when both emulgel and cream formulations were compared; the emulgels enhanced the delivery of pravastatin more than the creams. PMID:26505148

  5. Fentanyl-Laced 'Norco' Is Lethal, Report Warns

    MedlinePlus

    ... fullstory_160158.html Fentanyl-Laced 'Norco' Is Lethal, Report Warns New street drug combines two synthetic opioids ... imprint and were beige instead of white. The report was published online July 27 in the journal ...

  6. Development of patches for the controlled release of dehydroepiandrosterone.

    PubMed

    Minghetti, P; Cilurzo, F; Casiraghi, A; Montanari, L; Santoro, A

    2001-08-01

    Dehydroepiandrosterone (DHEA) and its sulfate conjugate (DHEAS) are the major secretory steroidal products of the adrenal gland. Some epidemiologic studies have found an association between low DHEA serum levels in patients and many important diseases. To prevent all such pathological conditions and, in any case, in aging, a DHEA supplementation has been proposed. DHEA shows a low oral bioavailability; taking the bioavailability obtained by the subcutaneous route as 100%, it was estimated that the potencies of DHEA by the percutaneous and oral routes were approximately 33% and 3%, respectively. Thus, transdermal patches could be considered a promising formulation as a continuous and controlled delivery of DHEA in replacement therapy is desired. With the aim of evaluating the effect of the matrix composition in terms of polymers and enhancers on the DHEA skin permeation flux, 10 types of monolayer self-adhesive patches containing 0.25mg/cm2 of active ingredient were designed. The matrices were based on three different acrylic copolymers: an acrylate-vinylacetate copolymer, a polyaminomethylmethacrylate (PAMA), and a polymethylmethacrylate. Transcutol (TR), mint essential oil, Lauroglycol, Brij 58, and propylene glycol (PG) were evaluated as DHEA skin permeation enhancers. All prepared patches were characterized by drug content, light microscopy, and in vitro skin permeation, performed using a modified Franz-type diffusion cell and human stratum corneum and epidermis as a membrane. The in vitro skin permeation studies are particularly significant in the development studies of DHEA patches as the in vivo determination of DHEA is affected b the fact that the endogen substance in the plasma is not constant over time. Among the testedpatches, highest DHEA fluxes were obtained using the formulation based on PAMA. Moreover, the introduction in the matrix of binary mixtures of TR and PG, used also for their plasticizer properties, permitted enhancing DHEA skin permeation

  7. Transdermal delivery of Angiotensin Converting Enzyme inhibitors.

    PubMed

    Helal, Fouad; Lane, Majella E

    2014-09-01

    The Angiotensin Converting Enzyme (ACE) inhibitor class of drugs has been in clinical use since the 1970s for the management of all grades of heart failure, hypertension, diabetic nephropathy and prophylaxis of cardiovascular events. Because of the advantages associated with transdermal delivery compared with oral delivery many researchers have investigated the skin as a portal for administration of ACE inhibitors. This review summarises the various studies reported in the literature describing the development and evaluation of transdermal formulations of ACE inhibitors. Captopril, enalapril maleate, lisinopril dihydrate, perindopril erbumine and trandolapril are the most studied in connection with transdermal preparations. The methodologies reported are considered critically and the limitations of the various skin models used are also highlighted. Finally, opportunities for novel transdermal preparations of ACE inhibitor drugs are discussed with an emphasis on rational formulation design. PMID:24657822

  8. The pharmacokinetics of the β2-adrenoceptor agonist, tulobuterol, in Beagle dogs following transdermal and intravenous administration.

    PubMed

    Kim, J H; Kim, T H; Park, H J; Choi, Y J; Kang, J H; Song, K H; Koo, T S; Seo, K W

    2016-02-01

    Tulobuterol is a β2-adrenergic agonist that was the first bronchodilator approved as a transdermal patch for humans. Previous studies have examined the pharmacokinetics of tulobuterol in humans but not in the veterinary species. In this study, the pharmacokinetics of tulobuterol was examined in healthy Beagle dogs after transdermal and intravenous administration. The Cmax was 2.09 ng/mL at 16.0 h for a 0.2 mg/kg patch and 4.85 ng/mL at 13.6 h for a 0.4 mg/kg patch. The effective blood level in humans is 1-3 ng/mL, a concentration achieved using the 0.2 mg/kg patch in dogs. In conclusion, application of a 0.2 mg/kg tulobuterol patch to healthy dogs led to an apparently effective blood concentration for 24 h. PMID:26639828

  9. Selegiline Transdermal System (STS) as an Aid for Smoking Cessation

    PubMed Central

    Gorgon, Liza; Jones, Karen; McSherry, Frances; Glover, Elbert D.; Anthenelli, Robert M.; Jackson, Thomas; Williams, Jill; Murtaugh, Cristin; Montoya, Ivan; Yu, Elmer; Elkashef, Ahmed

    2012-01-01

    Introduction: This study examined the efficacy and safety of selegiline transdermal system (STS) and brief repeated behavioral intervention (BRBI) for smoking cessation in heavy smokers. We hypothesized that the quit rate of subjects who received STS and BRBI would be significantly greater than that of those who received placebo patch and BRBI. Methods: This was a double-blind, placebo-controlled parallel-group study in which 246 men and women were randomized to receive either STS (n = 121) or placebo patch (n =125) for 9 weeks. Recruitment targeted heavy smokers, defined as individuals with self-reported use of ≥15 cigarettes/day in the 30 days prior to enrollment, who had smoked cigarettes for the past 5 years, and had an expired CO level ≥9 ppm during screening. Results: Although STS was well tolerated, the overall results indicated that STS with BRBI was not more effective than placebo plus BRBI for smoking cessation (p = .58). Conclusions: The results are discussed in relation to interventions for heavy smokers. Although 2 trials using oral selegiline both showed trends toward improved abstinence, these results indicate that STS with BRBI was not an effective aid for smoking cessation at the end of treatment (10 weeks), 14, or 26 weeks. PMID:21846661

  10. Effect of fentanyl on baroreflex control of circumflex coronary conductance.

    PubMed

    Moore, P G; Quail, A W; Cottee, D B; McIlveen, S A; White, S W

    2000-12-01

    1. Fentanyl, a synthetic mciro-opioid receptor agonist, is the preferred induction and maintenance anaesthetic agent in cardiac surgery. 2. Its actions on myocardial blood flow are poorly understood. There are reports of intra-operative myocardial ischaemia. Its reported actions on cardiorespiratory control vary widely, but do involve hypertension, bradycardia and peripheral vasoconstriction. 3. Accordingly, the postulate that fentanyl would cause coronary vasoconstriction and myocardial disadvantage was examined in awake dogs with a continuous wave Doppler flow probe mounted on the circumflex coronary artery. 4. Continuous intravenous infusion of fentanyl citrate (550 ng/kg per min) raised plasma concentrations of fentanyl to 3.37 ng/mL in a linear fashion at 20 min. There was a fall in core temperature of 0.7 degrees C and, although no apparent depression of ventilation or fall in arterial or coronary sinus PO2, there was a rise in PCO2 and H+ concentration. Some dogs salivated and panted transiently. Thus, fentanyl may reset temperature regulation in low doses but, at higher doses, is associated with metabolic acidosis. 5. In sinus rhythm, the arterial pressure of the dogs fell slightly, then rose to 115% of resting control. Circumflex flow and conductance rose early, then conductance steadily declined to 83%. Heart rate fell, then rose before returning to pre-infusion levels. The early circumflex coronary vasodilator effects, but not the later vasoconstrictor effects, were reduced in dogs with paced hearts. 6. In dogs with paced hearts, a dose-effect study using 138, 275, 550 and 1100 ng/kg per min fentanyl suggested that, at low plasma concentrations of 1-2 ng/mL, vasodilatation does occur in both coronary and systemic circulations; however, at higher doses, intense coronary and systemic vasoconstriction supervenes. 7. The dose-response effect of fentanyl on arterial baroreflex control of circumflex conductance was examined during the immediate 8 s circumflex

  11. Transdermal delivery of therapeutic agent

    NASA Technical Reports Server (NTRS)

    Kwiatkowski, Krzysztof C. (Inventor); Hayes, Ryan T. (Inventor); Magnuson, James W. (Inventor); Giletto, Anthony (Inventor)

    2008-01-01

    A device for the transdermal delivery of a therapeutic agent to a biological subject that includes a first electrode comprising a first array of electrically conductive microprojections for providing electrical communication through a skin portion of the subject to a second electrode comprising a second array of electrically conductive microprojections. Additionally, a reservoir for holding the therapeutic agent surrounding the first electrode and a pulse generator for providing an exponential decay pulse between the first and second electrodes may be provided. A method includes the steps of piercing a stratum corneum layer of skin with two arrays of conductive microprojections, encapsulating the therapeutic agent into biocompatible charged carriers, surrounding the conductive microprojections with the therapeutic agent, generating an exponential decay pulse between the two arrays of conductive microprojections to create a non-uniform electrical field and electrokinetically driving the therapeutic agent through the stratum corneum layer of skin.

  12. The unique role of transdermal buprenorphine in the global chronic pain epidemic.

    PubMed

    Pergolizzi, Joseph V; Scholten, Willem; Smith, Kevin J; Leighton-Scott, James; Willis, Jenna C; Henningfield, Jack E

    2015-06-01

    Pain is a global epidemic, exacerbated by barriers to access of opioid analgesics. Regulations about opioids attempt to protect public health from the risks of harmful use of opioids, diversion, and dependence. Transdermal buprenorphine is an effective opioid analgesic agent with unique properties that may make it particularly well suited for more widespread use. It is a versatile analgesic product with demonstrated safety and effectiveness in cancer and noncancer pain populations. Its pharmacological properties make it a first-line opioid analgesic for geriatric patients and patients with renal dysfunction; no dosing adjustments need to be made. The 7-day transdermal delivery system is convenient for patients and promotes compliance. A low dose of buprenorphine can provide effective and well-tolerated pain relief. Although buprenorphine has been associated with certain opioid-related adverse effects, such as dizziness and nausea, it is associated with a lower rate of constipation than many other opioid analgesics. The potential for nonmedical use of buprenorphine is relatively low compared with other opioid agents. Buprenorphine has a relatively low likeability for nonmedical use and the transdermal matrix patch renders the substance particularly difficult to extract for illicit purposes. PMID:26205326

  13. Transdermal delivery of naltrexol and skin permeability lifetime after microneedle treatment in hairless guinea pigs

    PubMed Central

    Banks, Stan L.; Pinninti, Raghotham R.; Gill, Harvinder S.; Paudel, Kalpana S.; Crooks, Peter A.; Brogden, Nicole K.; Prausnitz, Mark R.; Stinchcomb, Audra L.

    2010-01-01

    Controlled-release delivery of 6-β-naltrexol (NTXOL), the major active metabolite of naltrexone, via a transdermal patch is desirable for treatment of alcoholism. Unfortunately, NTXOL does not diffuse across skin at a therapeutic rate. Therefore, the focus of this study was to evaluate microneedle (MN) skin permeation enhancement of NTXOL's hydrochloride salt in hairless guinea pigs. Specifically, these studies were designed to determine the lifetime of MN-created aqueous pore pathways. Microneedle pore lifetime was estimated by pharmacokinetic evaluation, transepidermal water loss (TEWL) and visualization of MN-treated skin pore diameters using light microscopy. A 3.6 fold enhancement in steady state plasma concentration was observed in vivo with MN treated skin with NTXOL·HCl, as compared to NTXOL base. TEWL measurements and microscopic evaluation of stained MN-treated guinea pig skin indicated the presence of pores, suggesting a feasible non-lipid bilayer pathway for enhanced transdermal delivery. Overall, MN-assisted transdermal delivery appears viable for at least 48 h after MN-application. PMID:20166200

  14. Increases in Fentanyl-Related Overdose Deaths - Florida and Ohio, 2013-2015.

    PubMed

    Peterson, Alexis B; Gladden, R Matthew; Delcher, Chris; Spies, Erica; Garcia-Williams, Amanda; Wang, Yanning; Halpin, John; Zibbell, Jon; McCarty, Carolyn Lullo; DeFiore-Hyrmer, Jolene; DiOrio, Mary; Goldberger, Bruce A

    2016-01-01

    In March and October 2015, the Drug Enforcement Administration (DEA) and CDC issued nationwide alerts identifying fentanyl, particularly illicitly manufactured fentanyl (IMF), as a threat to public health and safety (1,2). IMF is pharmacologically similar to pharmaceutical fentanyl (PF), but is unlawfully produced in clandestine laboratories, obtained via illicit drug markets, and includes fentanyl analogs. Fentanyl is a synthetic opioid 50-100 times more potent than morphine and approved for the management of surgical/postoperative pain, severe chronic pain, and breakthrough cancer pain.* DEA's National Forensic Laboratory Information System (NFLIS) collects drug identification results from drug cases analyzed by federal, state, and local forensic laboratories throughout the United States.(†) In 2014, 80% of fentanyl submissions (i.e., drug products obtained by law enforcement that tested positive for fentanyl) in NFLIS were identified from 10 states, including Florida and Ohio (2), and seven of these 10 states reported sharp increases in fentanyl-related overdose deaths (fentanyl deaths) (3). This report presents findings of increased fentanyl deaths during 2013-2015 from investigations conducted by the University of Florida and the Ohio Department of Public Health, in collaboration with CDC. Analyses examined the association between trends in fentanyl-related law enforcement submissions and fentanyl deaths and describes groups at risk for fentanyl death using medical examiner and coroner reports. The marked increases in fentanyl death in Florida and Ohio during 2013-2015 were closely associated with parallel increases in fentanyl submissions, with the largest impact on persons who use heroin, consistent with reports that IMF is commonly mixed with or sold as heroin (1,4). In Ohio, circumstances associated with fentanyl deaths included a current diagnosed mental health disorder(§) and recent release from an institution such as a jail, rehabilitation facility

  15. Relative Bioavailability of Fentanyl Following Various Dosing Regimens of Fentanyl Buccal Tablet in Healthy Japanese Volunteers

    PubMed Central

    Darwish, Mona; Tempero, Kenneth; Jiang, John G; Simonson, Philip G

    2008-01-01

    Background Fentanyl buccal tablet (FBT; FENTORA®, Cephalon, Inc., Frazer, PA, USA) is indicated in the US for breakthrough pain in patients with cancer who are already receiving and are tolerant to around-the-clock opioid therapy for underlying persistent cancer pain. For each individual patient, FBT should be titrated to the effective dose. Objective The primary objective was to characterize the pharmacokinetic parameters of FBT 400 µg administered as a single 400 µg tablet (regimen A) or as two 200 µg tablets given simultaneously (regimen B) and determine whether these are bioequivalent in healthy Japanese volunteers. Regimen C (two 200 µg tablets 30 minutes apart) was also compared as a secondary objective. Methods Healthy Japanese adults received regimens A, B, and C in a crossover fashion. Naltrexone was given to minimize the opioid effects of fentanyl. Serum fentanyl concentrations were determined in venous blood collected through 36 hours post dose. Regimens were declared bioequivalent with respect to bioavailability (as reflected by AUC0–∞, AUC0–last, and Cmax) if the 90% confidence interval (CI) of the regimens' ratio fell within 0.80–1.25 (80%–125%). Results Twenty-nine volunteers (13 men, 16 women) were enrolled; 24 completed the study. Regimens A and B had bioequivalent systemic exposure parameters (B/A [90% CI]: AUC0–∞108.4 [103.4, 113.7], AUC0–last 106.1 [100.7, 111.7], and Cmax 92.3 [83.2, 102.4]). Regimen C was bioequivalent to both A and B for AUCs, but only to B for Cmax. Median time to Cmax was 45 minutes for regimen A and 60 minutes for regimens B and C. The most frequent AEs were dizziness, application-site erythema, headache, somnolence, nausea, and vomiting. All AEs were mild or moderate. Conclusions Bioavailability of fentanyl after FBT 400 µg administered as a single tablet was bioequivalent to that after 2 simultaneously administered 200 µg tablets in healthy Japanese volunteers. AEs were mild or moderate. PMID

  16. Interindividual variation in transdermal and oral drug deliveries.

    PubMed

    Levin, Jacquelyn; Maibach, Howard

    2012-11-01

    It is generally assumed that the topical absorption of drugs is subject to more interindividual variation than the oral absorption of drugs. To date, we are unaware of any clinical studies or meta-analyses that compare the interindividual variation of transdermal and oral drug deliveries for a large number of medications. In this research article, the absorption data for 10 medications that can be used as an oral medication or a transdermal patch were compiled, and from the collected data, the interindividual variance was calculated for topical and oral absorption as an overall average and by drug. This research article also briefly reviews the pharmacokinetics and pharmacodynamics of transdermal and oral drug absorption. Our results indicate that there is considerable interindividual variation in topical and oral absorption for the 10 medications investigated. Yet, surprisingly, the calculated overall mean and median coefficient of variation (CV) for topical and oral absorption were comparable (within 10% of each other). Therefore, the interindividual variation in topical and oral absorption may not be as divergent as assumed previously. In a drug-by-drug comparison, certain medications demonstrated considerably more variation when absorbed orally versus topically and vice versa. It is unclear why certain drugs had less variation in absorption when delivered topically versus orally (or vice versa). However, patterns in drug molecular weight (MW) or octanol partition coefficient (log K(OCT) ) could not totally explain these findings. In our analysis, the previously reported correlation between MW or log K(OCT) and interindividual variation in absorption could only be replicated when plotting the topical absorption CV and MW. What became clear from our analysis is that the drug itself is an important variable when considering which route of delivery (oral or topical) will provide the least amount of interindividual variation. Our study had many limitations because

  17. A Comparison of the Effects of Transdermal Estradiol and Estradiol Valerate on Endometrial Receptivity in Frozen-thawed Embryo Transfer Cycles: A Randomized Clinical Trial

    PubMed Central

    Davar, Robab; Janati, Sima; Mohseni, Fereshteh; Khabazkhoob, Mehdi; Asgari, Soheila

    2016-01-01

    Background: The purpose of this study was to determine the optimal endometrial preparation protocol by comparing the clinical outcome of two methods of endometrial preparation in frozen-thawed embryo transfer (FET) cycles, including that is, oral estradiol and 17ß-estradiol transdermal patch. Methods: In this randomized controlled trial, women underwent either conventional IVF or intracytoplasmic sperm injection (ICSI) who had at least two top-quality embryos appropriate for cryopreservation and frozen embryos from previous cycles. In the study group (n=45), 17-B estradiol transdermal patches 100 μg were applied from the second day of the cycle and continued every other day. Then, each patch was removed after four days. In the control group (n=45), oral estradiol valerate 6 mg was started at the same time and continued daily. Results: There was a significant difference in estradiol level on the day of progesterone administration and the day of embryo transfer between the two groups (p= 0.001 in both), but no significant difference was observed between them in biochemical and clinical pregnancy rates (32.6% vs. 33.3%, p=1.000 and 30.2% vs. 33.3%, p=0.810, respectively). Conclusion: It is suggested that estradiol transdermal patches be used instead of oral estradiol in FET cycles. Due to the reduced costs, drug dose, and emotional stress as well as the simplicity of the protocol for patients. PMID:27141464

  18. Epidural Analgesia With Bupivacaine and Fentanyl Versus Ropivacaine and Fentanyl for Pain Relief in Labor: A Meta-Analysis.

    PubMed

    Guo, Shanbin; Li, Bo; Gao, Chengjie; Tian, Yue

    2015-06-01

    The aim of this study was to compare the efficacy and safety of the combinational use of bupivacaine and fentanyl versus ropivacaine and fentanyl in epidural analgesia for labor. Multiple electronic databases were searched by using appropriate MeSH terms, and keywords for original research papers published before October 2014. Meta-analyses were based on mean differences between the groups as well as odds ratios. Statistical heterogeneity was tested by I² index. Fifteen randomized controlled trials, recruiting 2097 parturient mothers overall, were selected for the meta-analyses. Concentrations of the preparations used (weight/volume; mean and standard deviations) were bupivacaine 0.1023% ± 0.0375%, ropivacaine 0.1095% ± 0.042%, and fentanyl 0.00021% ± 0.000089%. There were no statistically significant differences between both the combinations in the mean change in Visual Analog Score for pain during labor, incidence of instrumental or cesarean delivery, neonate Apgar score of <7, maternal satisfaction, duration of either first or second stage of labor, oxytocin use for induction, onset of analgesia, and duration of analgesia. Women who received ropivacaine and fentanyl had significantly lower incidence of motor blocks (odds ratio [95% CI] = 0.38 [0.30, 0.48] P < 0.00001, fixed effect and 0.38 [0.27, 0.54] P < 0.0001, random effects I² 30%) when compared with women who received bupivacaine and fentanyl. Incidence of side effects was similar for both the combinations. Analgesia with ropivacaine in combination with fentanyl at 0.1%:0.0002% ratio for labor pain relief is associated with lower incidence of motor blocks in comparison with analgesia with bupivacaine and fentanyl at similar ratio (0.1%: 0.0002%). PMID:26061307

  19. Transdermal Delivery of Nisoldipine: Refinement of Vehicles.

    PubMed

    El Maghraby, Gamal M; Ahmed, Amal A; Osman, Mohamed A

    2015-01-01

    Nisoldipine is used for the treatment of hypertension and angina pectoris. However, it has very low bioavailabil-ty, which is attributed to extensive pre-systemic metabolism. In addition, nisol-ipine is highly potent (used at a low dose). Taking into consideration the fact that transdermal delivery avoids the pre-systemic metabolism and is only suit-ble for potent drugs, nisoldipine can be considered as an excellent candidate for transdermal delivery. Accordingly, the purpose of this study was to optimize nisoldipine transdermal delivery. That was achieved initially by investigating the effect of vehicles on skin penetration. The tested vehicles were ranked with respect to transdermal flux of nisoldipine as isopropyl myristate > oleic acid > propylene glycol > water > polyethylene glycol 400. A combination of oleic acid with propylene glycol was synergistic with a ratio of 1:2 w/w being the best. These results were taken further to develop microemulsion systems using either oleic acid or isopropyl myristate as the oil phase. Both cases employed polyoxy-thylene sorbitan monooleate as a surfactant with propylene glycol being uti-ized as a cosurfactant in the case of oleic acid and ethanol in the case of isopropyl myristate. The developed microemulsions produced significant enhancement in nisoldipine transdermal delivery with the flux being even greater than that obtained from the corresponding pure vehicles. This achieve-ent was recorded in optimum microemulsion formulations which contained a cosurfactant. The study provided stepwise optimization of a vehicle for trans-ermal delivery of nisoldipine. PMID:26685495

  20. Permeation enhancer strategies in transdermal drug delivery.

    PubMed

    Marwah, Harneet; Garg, Tarun; Goyal, Amit K; Rath, Goutam

    2016-01-01

    Today, ∼74% of drugs are taken orally and are not found to be as effective as desired. To improve such characteristics, transdermal drug delivery was brought to existence. This delivery system is capable of transporting the drug or macromolecules painlessly through skin into the blood circulation at fixed rate. Topical administration of therapeutic agents offers many advantages over conventional oral and invasive techniques of drug delivery. Several important advantages of transdermal drug delivery are prevention from hepatic first pass metabolism, enhancement of therapeutic efficiency and maintenance of steady plasma level of the drug. Human skin surface, as a site of drug application for both local and systemic effects, is the most eligible candidate available. New controlled transdermal drug delivery systems (TDDS) technologies (electrically-based, structure-based and velocity-based) have been developed and commercialized for the transdermal delivery of troublesome drugs. This review article covers most of the new active transport technologies involved in enhancing the transdermal permeation via effective drug delivery system. PMID:25006687

  1. Transdermal Photopolymerization for Minimally Invasive Implantation

    NASA Astrophysics Data System (ADS)

    Elisseeff, J.; Anseth, K.; Sims, D.; McIntosh, W.; Randolph, M.; Langer, R.

    1999-03-01

    Photopolymerizations are widely used in medicine to create polymer networks for use in applications such as bone restorations and coatings for artificial implants. These photopolymerizations occur by directly exposing materials to light in "open" environments such as the oral cavity or during invasive procedures such as surgery. We hypothesized that light, which penetrates tissue including skin, could cause a photopolymerization indirectly. Liquid materials then could be injected s.c. and solidified by exposing the exterior surface of the skin to light. To test this hypothesis, the penetration of UVA and visible light through skin was studied. Modeling predicted the feasibility of transdermal polymerization with only 2 min of light exposure required to photopolymerize an implant underneath human skin. To establish the validity of these modeling studies, transdermal photopolymerization first was applied to tissue engineering by using "injectable" cartilage as a model system. Polymer/chondrocyte constructs were injected s.c. and transdermally photopolymerized. Implants harvested at 2, 4, and 7 weeks demonstrated collagen and proteoglycan production and histology with tissue structure comparable to native neocartilage. To further examine this phenomenon and test the applicability of transdermal photopolymerization for drug release devices, albumin, a model protein, was released for 1 week from photopolymerized hydrogels. With further study, transdermal photpolymerization potentially could be used to create a variety of new, minimally invasive surgical procedures in applications ranging from plastic and orthopedic surgery to tissue engineering and drug delivery.

  2. A Survey of Patch Methods

    NASA Technical Reports Server (NTRS)

    Barnhill, R. E.

    1985-01-01

    Patch methods are someshow a response to the fact that surface geometry is local, that is, only small parts of a surface are created at a time. The two categories of patches, transfinite patches and finite dimensional patches are examined and a discussion of trivariate patches is presented.

  3. Once-daily transdermal rivastigmine in the treatment of Alzheimer’s disease

    PubMed Central

    Wentrup, Andreas; Oertel, Wolfgang H; Dodel, Richard

    2008-01-01

    During the past decade, transdermal delivery systems (TDS) have become increasingly important for treating neurologic and psychiatric disorders. The rivastigmine patch was the first patch to be approved to treat Alzheimer’s disease (AD). The 9.5 mg/24 h patch has equal efficacy to the capsules and reduces gastrointestinal adverse events, such as nausea and vomiting, by two-thirds. This treatment is well tolerated by patients because drug delivery is even and continuous, reducing fluctuation in drug plasma level, and attenuating the development of centrally mediated cholinergic side effects. Furthermore, once-a-day application of the patch enables an easy treatment schedule, ease of handling, infrequent skin irritations, and a patient- and caregiver-friendly mode of administration. Improved compliance with a subsequent drug administration may contribute to better clinical efficacy, reduce caregiver burden, result in a slower rate of institutionalization, and lead to a decrease in healthcare and medical costs. Because of these advantages, the rivastigmine patch has enabled great progress in the treatment of AD, and represents an excellent alternative to the orally administered cholinesterase inhibitors. PMID:19920911

  4. Crystallization of beta-estradiol in an acrylic transdermal drug delivery system.

    PubMed

    Variankaval, N E; Jacob, K I; Dinh, S M

    1999-03-15

    Transdermal drug delivery systems are pharmaceutical products that can deliver controlled doses of drugs from polymeric patches applied on the human skin. The long-term stability of these patches is a critical issue relative to their performance in delivering drugs at a constant rate. Where a drug has been dissolved in the polymeric adhesive patch, crystallization has been reported in several systems. This study uses a variety of characterization tools to determine the physical and chemical nature of the precipitates formed in situ in estradiol patches. Optical microscopy revealed that crystals were formed in a single layer inside the adhesive matrix and that there were two distinctly different morphologies: needle-like crystals and aggregates around the needles. From IR measurements it was evident that estradiol probably was present in more than one crystal form in these patches. Raman microscopy showed that the needle-like crystals contain the adhesive component and the aggregates some modified crystal form of estradiol, indicating that in addition to the drug, the polymeric adhesive also crystallizes during storage. PMID:10397943

  5. Permeation study of indomethacin from polycarbazole/natural rubber blend film for electric field controlled transdermal delivery.

    PubMed

    Thorngkham, Pornwalai; Paradee, Nophawan; Niamlang, Sumonman; Sirivat, Anuvat

    2015-05-01

    Transdermal drug delivery is an alternative route to transport the drug into the blood system. This method has been continuously developed to overcome limitations and is now suitable for a wide variety of drug molecules. In this work, the influences of electric field and conductive polymer were investigated for developing a unique drug delivery system from double-centrifuged natural rubber (DCNR) matrix. Indomethacin (IN) was loaded into polycarbazole (PCz) as a conductive polymer drug host to promote the efficient transportation of the drug. The IN-loaded PCz was blended with DCNR to form a transdermal patch. The permeation of IN through the PCz/NR film and pig skin was carrried out by a modified Franz diffusion cell. The IN diffused from DCNR film by the diffusion controlled combined with erosion mechanism depending on the pore formation period. The drug permeation increased with decreasing cross-link ratio because of more accessible pathways for the drug permeation. Moreover, an electric field and the inclusion of PCz as the drug carrier dramatically improved the diffusion of the drug from the membrane by through the electrorepulsive force and electro-reduced PCz expansion. Thus, the PCz/DCNR films are shown here as a potential transdermal patch under applied electric field. PMID:25754446

  6. Transdermal delivery of heparin: Physical enhancement techniques.

    PubMed

    Ita, Kevin

    2015-12-30

    Thromboembolic complications are the most common preventable cause of mortality and morbidity in trauma patients. Thrombosis is also the common cause of ischemic heart disease (acute coronary syndrome), stroke, and venous thromboembolism. Heparin, as a potent anticoagulant, has been used in clinical practice for more than five decades and remains the major medicine for the prevention and treatment of venous thromboembolism. However it binds to the endothelium and has a high affinity for plasma proteins resulting in a short half-life and unpredictable bioavailability. Transdermal drug delivery can address the problems of short half-life and unpredictable bioavailability. Other advantages of transdermal drug delivery include convenience, improved patient compliance, prompt termination of dosing and avoidance of the first-pass effect. This review focuses on different approaches used for transdermal delivery of heparin. PMID:26611668

  7. An update on pharmacological, pharmacokinetic properties and drug-drug interactions of rotigotine transdermal system in Parkinson's disease and restless legs syndrome.

    PubMed

    Elshoff, Jan-Peer; Cawello, Willi; Andreas, Jens-Otto; Mathy, Francois-Xavier; Braun, Marina

    2015-04-01

    This narrative review reports on the pharmacological and pharmacokinetic properties of rotigotine, a non-ergolinic D₃/D₂/D₁ dopamine receptor agonist approved for the treatment of early- and advanced-stage Parkinson's disease (PD) and moderate to severe restless legs syndrome (RLS). Rotigotine is formulated as a transdermal patch providing continuous drug delivery over 24 h, with a plasma concentration profile similar to that of administration via continuous intravenous infusion. Absolute bioavailability after 24 h transdermal delivery is 37 % of the applied rotigotine dose. Following a single administration of rotigotine transdermal system (24-h patch-on period), most of the absorbed drug is eliminated in urine and feces as sulphated and glucuronidated conjugates within 24 h of patch removal. The drug shows a high apparent volume of distribution (>2500 L) and a total body clearance of 300-600 L/h. Rotigotine transdermal system provides dose-proportional pharmacokinetics up to supratherapeutic dose rates of 24 mg/24 h, with steady-state plasma drug concentrations attained within 1-2 days of daily dosing. The pharmacokinetics of rotigotine transdermal patch are similar in healthy subjects, patients with early- or advanced-stage PD, and patients with RLS when comparing dose-normalized area under the plasma concentration-time curve (AUC) and maximum plasma drug concentration (Cmax), as well as half-life and other pharmacokinetic parameters. Also, it is not influenced in a relevant manner by age, sex, ethnicity, advanced renal insufficiency, or moderate hepatic impairment. No clinically relevant drug-drug interactions were observed following co-administration of rotigotine with levodopa/carbidopa, domperidone, or the CYP450 inhibitors cimetidine or omeprazole. Also, pharmacodynamics and pharmacokinetics of an oral hormonal contraceptive were not influenced by rotigotine co-administration. Rotigotine was generally well tolerated, with an adverse event profile

  8. Pharmacokinetics, safety, and tolerability of rotigotine transdermal system in healthy Japanese and Caucasian subjects following multiple-dose administration.

    PubMed

    Cawello, Willi; Kim, Seong Ryul; Braun, Marina; Elshoff, Jan-Peer; Masahiro, Takeuchi; Ikeda, Junji; Funaki, Tomoo

    2016-08-01

    Rotigotine is a dopamine receptor agonist indicated for the treatment of Parkinson's disease and moderate-to-severe restless legs syndrome. Continuous transdermal delivery of rotigotine via a silicon-based patch maintains stable plasma concentrations over 24 h. The objective of the study was to evaluate the pharmacokinetics, safety, and tolerability of a multiple-dose schedule of rotigotine transdermal patch in Japanese and Caucasian subjects. In this open-label, repeated-dose, parallel-group study (ClinicalTrials.gov: NCT01854216), healthy male and female subjects of Japanese or Caucasian ethnic origin were matched by gender, body mass index, and age. Subjects underwent a 9-day patch application period. 12 Japanese and 12 Caucasian subjects were included in the pharmacokinetic analyses. Mean apparent doses (actual amount of drug delivered) increased proportionally with rotigotine nominal dosages (1, 2, and 4 mg/24 h) and were similar for both ethnic groups, with large inter-individual variability. Mean plasma concentration-time profiles for unconjugated rotigotine were similar in both ethnic groups at day 3 for each dosage. Peak concentrations (C max,ss) and area under the concentration-time curves from pre-dose to the concentration measured 24 h after administration of patch (AUC(0-24,ss)) showed similar exposure in both groups; higher values in Japanese subjects were explained by differences in body weight. For total rotigotine, C max,ss and AUC(0-24,ss) values were higher in Caucasian subjects and could be explained by small differences in apparent dose. Rotigotine was generally well tolerated following multiple applications up to 4 mg/24 h. These findings suggest similar dosage requirements for rotigotine transdermal system in Japanese and Caucasian populations. PMID:25773763

  9. The fentanyl 'lozenge' story: from books to battlefield.

    PubMed

    Aldington, Dominic; Jagdish, S

    2014-06-01

    This article outlines the process that led to the introduction of the fentanyl lozenge for acute pain management. It starts with the historical context before discussing the recognition of an ongoing problem and then identifies the options that were considered. There follows a description of the pharmacology of fentanyl before describing the trial of concept that was conducted. This leads into an outline of the meetings and committees that had to be engaged with before the final acceptance and subsequent ushering in. The final section describes an option that was unsuccessful. PMID:24413475

  10. An Efficient, Optimized Synthesis of Fentanyl and Related Analogs

    PubMed Central

    Valdez, Carlos A.; Leif, Roald N.; Mayer, Brian P.

    2014-01-01

    The alternate and optimized syntheses of the parent opioid fentanyl and its analogs are described. The routes presented exhibit high-yielding transformations leading to these powerful analgesics after optimization studies were carried out for each synthetic step. The general three-step strategy produced a panel of four fentanyls in excellent yields (73–78%) along with their more commonly encountered hydrochloride and citric acid salts. The following strategy offers the opportunity for the gram-scale, efficient production of this interesting class of opioid alkaloids. PMID:25233364

  11. Additive effect of propofol and fentanyl precipitating cardiogenic shock

    PubMed Central

    Prabhakaran, AC Jesudoss

    2013-01-01

    The intravenous administration of propofol and fentanyl has become a common practice in a variety of clinical settings including outpatient dermatologic, cosmetic and oral surgery. The combination provides both systematic sedation and analgesia with low incidence of unwanted side effects. The cardiogenic shock is very uncommon in healthy individuals. The cardiovascular depressive effect of propofol and fentanyl has been well established, but the development of cardiogenic shock is very rare when these drugs are used together. Hence the awareness of this effect is advantageous to the patients undergoing such surgeries PMID:23960431

  12. Transdermal Insulin Delivery Using Microdermabrasion

    PubMed Central

    Andrews, Samantha; Lee, Jeong Woo; Choi, Seong-O

    2011-01-01

    Purpose Transdermal insulin delivery is an attractive needle-free alternative to subcutaneous injection conventionally used to treat diabetes. However, skin’s barrier properties prevent insulin permeation at useful levels. Methods We investigated whether microdermabrasion can selectively remove skin’s surface layers to increase skin permeability as a method to administer insulin to diabetic rats. We further assessed the relative roles of stratum corneum and viable epidermis as barriers to insulin delivery. Results Pretreatment of skin with microdermabrasion to selectively remove stratum corneum did not have a significant effect on insulin delivery or reduction in blood glucose level (BGL). Removal of full epidermis by microdermabrasion significantly reduced BGL, similar to the positive control involving subcutaneous injection of 0.1U insulin. Significant pharmacokinetic differences between microdermabrasion and subcutaneous injection were faster time to peak insulin concentration after injection and larger peak insulin concentration and area-under-the-curve after microdermabrasion. Conclusions Microdermabrasion can increase skin permeability to insulin at levels sufficient to reduce BGL. Viable epidermis is a barrier to insulin delivery such that removal of full epidermis enables significantly more insulin delivery than removal of stratum corneum alone. PMID:21499837

  13. Transdermal clonidine in patients with swallowing dysfunction.

    PubMed

    Goldenberg, Gregory; Bharathan, Thayyullathil; Shifrin, Inna

    2014-09-01

    Patients with swallowing dysfunction are usually very ill and have a constellation of challenging issues requiring palliation. Accumulation of oropharyngeal secretions leads to a substantial effort of medical teams including doctors, nurses, respiratory therapists, and ancillary staff. We present 10 patients successfully treated with application of transdermal clonidine film. It was well tolerated, provided quick control of secretions, and reduced staff labor. We suggest that transdermal clonidine can be used as antisialogogue in patients with swallowing dysfunction. Clonidine pharmacology is physiologic grounds for this clinical application. PMID:24813023

  14. Ultrasound-Mediated Transdermal Protein Delivery

    NASA Astrophysics Data System (ADS)

    Mitragotri, Samir; Blankschtein, Daniel; Langer, Robert

    1995-08-01

    Transdermal drug delivery offers a potential method of drug administration. However, its application has been limited to a few low molecular weight compounds because of the extremely low permeability of human skin. Low-frequency ultrasound was shown to increase the permeability of human skin to many drugs, including high molecular weight proteins, by several orders of magnitude, thus making transdermal administration of these molecules potentially feasible. It was possible to deliver and control therapeutic doses of proteins such as insulin, interferon γ, and erythropoeitin across human skin. Low-frequency ultrasound is thus a potential noninvasive substitute for traditional methods of drug delivery, such as injections.

  15. Vitamin B12 loaded polycaprolactone nanofibers: a novel transdermal route for the water soluble energy supplement delivery.

    PubMed

    Madhaiyan, Kalaipriya; Sridhar, Radhakrishnan; Sundarrajan, Subramanian; Venugopal, Jayarama Reddy; Ramakrishna, Seeram

    2013-02-28

    Biocompatible PCL polymer nanofiber mediated sustained release of hydrophilic drug and applicability as transdermal delivery system is attempted. This new attempt to investigate water soluble vitamin delivery with hydrophobic polymer nanofiber sustained the release of the vitamin and the method is suited for the transdermal patch applications. The drug loaded fibers were characterized with SEM for morphology, porometer for pore size measurements, mechanical strength calculation and FT-IR for drug load characterization. The contact angle measurement showed surface wettability and controlled release of drug was quantified with UV absorption measurements. To further enhance the release of vitamin, the polymer fiber was plasma treated at different time intervals and made hydrophilic gradually. Since the increased surface area and drug encapsulation in nano-reservoirs can able to release drug in small quantities and in a sustained manner we attempted the release of the energy supplement with nanofibrous delivery mode. PMID:23370432

  16. FNAL system patching design

    SciTech Connect

    Schmidt, Jack; Lilianstrom, Al; Romero, Andy; Dawson, Troy; Sieh, Connie; /Fermilab

    2004-01-01

    FNAL has over 5000 PCs running either Linux or Windows software. Protecting these systems efficiently against the latest vulnerabilities that arise has prompted FNAL to take a more central approach to patching systems. Due to different levels of existing support infrastructures, the patching solution for linux systems differs from that of windows systems. In either case, systems are checked for vulnerabilities by Computer Security using the Nessus tool.

  17. DyninstAPI Patches

    Energy Science and Technology Software Center (ESTSC)

    2012-04-01

    We are seeking a code review of patches against DyninstAPI 8.0. DyninstAPI is an open source binary instrumentation library from the University of Wisconsin and University of Maryland. Our patches port DyninstAPI to the BlueGene/P and BlueGene/Q systems, as well as fix DyninstAPI bugs and implement minor new features in DyninstAPI.

  18. Tunable circular patch antennas

    NASA Astrophysics Data System (ADS)

    Lan, G.-L.; Sengupta, D. L.

    1985-10-01

    A method to control the resonant or operating frequencies of circular patch antennas has been investigated experimentally and theoretically. It consists of the placement of passive metallic or tuning posts at approximate locations within the input region of the antenna. Comparison of measured and analytical results seems to establish the validity of a theoretical model proposed to determine the input performance of such circular patch antennas.

  19. Nortriptyline for smoking cessation: release and human skin diffusion from patches.

    PubMed

    Melero, A; Garrigues, T M; Alós, M; Kostka, K H; Lehr, C M; Schaefer, U F

    2009-08-13

    The objective of this work was to develop a simple and inexpensive transdermal formulation containing Nortriptyline Hydrochloride (NTH) for smoking cessation support therapy. Hydroxypropyl-methyl-cellulose was chosen as polymer and a mixture of transdermal enhancers (selected from previous research) was incorporated. The formulations were characterised in terms of appearance, thickness, uniformity of NTH content, release and skin permeation. Release studies demonstrated controlled release for four formulations. Diffusion studies were performed through human heat separated epidermis (HHSE) using Franz Diffusion Cells (FDC). Patches provided different fluxes varying from 20.39+/-7.09 microg/(cm(2) h) to 256.19+/-94.62 microg/(cm(2) h). The penetration profiles of NTH within the stratum corneum (SC) and deeper skin layers (DSL) were established after three administration periods (3 h, 6 h, and 24 h). Skin changes induced by the application of the patches were observed by confocal laser scanning microscopy (CLSM). The highest flux obtained would provide the recommended doses for smoke cessation support therapy (25-75 mg per day) with a 2 cm x 2 cm patch or a 3.5 cm x 3.5 cm patch, respectively, without skin damage evidence. PMID:19501148

  20. Perspectives on transdermal ultrasound mediated drug delivery

    PubMed Central

    Smith, Nadine Barrie

    2007-01-01

    The use of needles for multiple injection of drugs, such as insulin for diabetes, can be painful. As a result, prescribed drug noncompliance can result in severe medical complications. Several noninvasive methods exist for transdermal drug delivery. These include chemical mediation using liposomes and chemical enhancers or physical mechanisms such as microneedles, iontophoresis, electroporation, and ultrasound. Ultrasound enhanced transdermal drug delivery offers advantages over traditional drug delivery methods which are often invasive and painful. A broad review of the transdermal ultrasound drug delivery literature has shown that this technology offers promising potential for noninvasive drug administration. From a clinical perspective, few drugs, proteins or peptides have been successfully administered transdermally because of the low skin permeability to these relatively large molecules, although much work is underway to resolve this problem. The proposed mechanism of ultrasound has been suggested to be the result of cavitation, which is discussed along with the bioeffects from therapeutic ultrasound. For low frequencies, potential transducers which can be used for drug delivery are discussed, along with cautions regarding ultrasound safety versus efficacy. PMID:18203426

  1. Immune modulation using transdermal photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Levy, Julia G.; Chowdhary, R. K.; Ratkay, Leslie G.; Waterfield, Douglas; Obochi, Modestus; Leong, Simon; Hunt, David W. C.; Chan, Agnes H.

    1995-01-01

    The photosensitizer benzoporphyrin derivative monoacid ring A (VerteporfinR or BPD) has maximum absorption characteristics (690 nm) and biodistribution characteristics which permit activation of the drug in capillaries of the skin without causing skin photosensitivity (transdermal PDT). This permits targeting of cells in the circulation for selective ablation. Since BPD has been shown to accumulate preferentially in activated lymphocytes and monocytes, studies have been undertaken to determine the effect of transdermal PDT on murine models for rheumatoid arthritis (the MRL/lpr adjuvant enhanced model) and multiple sclerosis (the experimental allergic encephalomyelitis (EAE) model in PL mice). Localized transdermal PDT with BPD was found to be completely successful in preventing the development of adjuvant enhanced arthritis in the MRL/lpr mouse as well as improving the underlying arthritic condition of these animals. In the EAE model, in which an adoptive transfer system was used, it was found that transdermal PDT of recipients was effective in preventing EAE if treatments were implemented up to 24 hours after cell transfer but was not effective if given later, indicating the requirement for circulating T cells for effective treatment.

  2. [Fentanyl in peridural obstetrical analgesia. Evaluation after 4 years' use].

    PubMed

    Lévêque, C; Garen, C; Pathier, D; Mazuir, E; Maneglia, R; Janse-Marec, J; Cousin, M T

    1987-01-01

    7,500 deliveries occurred from the date of opening of the Maternity Hospital Jean-Rostand. 3,500 of these were conducted under epidural anaesthesia. At different stages prospective studies were carried out to recall the effect of adding fentanyl to bupivacaine when the epidural injection was made. A pharmacokinetic study. This shows that the levels in the mother and the fetus begin to coincide more with the number of doses that are given and pass from 0.3 after 50 micrograms have been administered to 0.5 after 100 micrograms have been administered and 0.7 after 150 micrograms have been administered. The fetal levels are far lower than those required to depress respiration. The half life of distribution through the circulation has been worked out at 4 minutes and the half for elimination of the drug at 460 minutes. The maternal levels show great fluctuations and late alterations. Analgesia is earlier, more complete and more prolonged when fentanyl is added. Fentanyl also masks irregularities. Undesirable effects such as tiredness, pruritus, nausea, vomiting and urinary retention occur infrequently and last only for short periods of time. No mother had respiratory depression. The doses of bupivacaine that had to be given were as a whole less when fentanyl was added. In 40% of cases it only required one injection to achieve analgesia throughout the whole labour. The length of labour and the number of caesarean operations carried out did not change.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3584862

  3. Pulmonary administration of aerosolised fentanyl: pharmacokinetic analysis of systemic delivery

    PubMed Central

    Mather, Laurence E; Woodhouse, Annie; Ward, M Elizabeth; Farr, Stephen J; Rubsamen, Reid A; Eltherington, Lorne G

    1998-01-01

    Aims Pulmonary drug delivery is a promising noninvasive method of systemic administration. Our aim was to determine whether a novel breath-actuated, microprocessor-controlled metered dose oral inhaler (SmartMist™, Aradigm Corporation) could deliver fentanyl in a way suitable for control of severe pain. Methods Aersolised pulmonary fentanyl base 100–300 μg was administered to healthy volunteers using SmartMist™ and the resultant plasma concentration-time data were compared with those from the same doses administered by intravenous (i.v.) injection in the same subjects. Results Plasma concentrations from SmartMist™ were similar to those from i.v. injection. Time-averaged bioavailability based upon nominal doses averaged 100%, and was >50% within 5 min of delivery. Fentanyl systemic pharmacokinetics were similar to those previously reported with no trends to dose-dependence from either route. Side-effects (e.g. sedation, lightheadedness) were the same from both routes. Conclusions Fentanyl delivery using SmartMist™ can provide analgetically relevant plasma drug concentrations. This, combined with its ease of noninvasive use and transportability, suggests a strong potential for field and domicilliary use, and for patient controlled analgesia without the need for i.v. cannulae. PMID:9690947

  4. Transdermal Delivery Devices: Fabrication, Mechanics and Drug Release from Silk**

    PubMed Central

    Raja, Waseem K.; MacCorkle, Scott; Diwan, Izzuddin M.; Abdurrob, Abdurrahman; Lu, Jessica; Omenetto, Fiorenzo G.; Kaplan, David L.

    2013-01-01

    Microneedles are a relatively simple, minimally invasive and painless approach to deliver drugs across the skin. However, there remain limitations with this approach because of the materials most commonly utilized for such systems. Silk protein, with tunable and biocompatibility properties, is a useful biomaterial to overcome the current limitations with microneedles. Silk devices preserve drug activity, offer superior mechanical properties and biocompatibility, can be tuned for biodegradability, and can be processed under aqueous, benign conditions. In the present work, we report the fabrication of dense microneedle arrays from silk with different drug release kinetics. The mechanical properties of the microneedle patches are tuned by post-fabrication treatments or by loading the needles with silk microparticles to increase capacity and mechanical strength. Drug release is further enhanced by the encapsulation of the drugs in the silk matrix and coating with a thin dissolvable drug layer. The microneedles are used on human cadaver skin and drugs were delivered successfully. The various attributes demonstrated suggest that silk-based microneedle devices can provide significant benefit as a platform material for transdermal drug delivery. PMID:23653252

  5. Effect of transdermal nicotine administration on exercise endurance in men.

    PubMed

    Mündel, Toby; Jones, David A

    2006-07-01

    Nicotine is widely reported to increase alertness, improve co-ordination and enhance cognitive performance; however, to our knowledge there have been no attempts to replicate these findings in relation to exercise endurance. The purpose of this study was to determine the effects nicotine might have on cycling endurance, perception of exertion and a range of physiological variables. With local ethics committee approval and having obtained informed consent, 12 healthy, non-smoking men (22 +/- 3 years; maximal O2 uptake, 56 +/- 6 ml kg(-1) min(-1), mean +/- s.d.) cycled to exhaustion at 18 degrees C and 65% of their peak aerobic power, wearing either a 7 mg transdermal nicotine patch (NIC) or a colour-matched placebo (PLA) in a randomized cross-over design; water was available ad libitum. Subjects were exercising at approximately 75% of their maximal O2 uptake with no differences in cadence between trials. Ten out of 12 subjects cycled for longer with NIC administration, and this resulted in a significant 17 +/- 7% improvement in performance (P < 0.05). No differences were observed for perceived exertion, heart rate or ventilation. There were no differences in concentrations of plasma glucose, lactate or circulating fatty acids. In the absence of any effect on peripheral markers, we conclude that nicotine prolongs endurance by a central mechanism. Possible modes of action are suggested. PMID:16627574

  6. Antinociceptive efficacy and plasma concentrations of transdermal buprenorphine in dogs.

    PubMed

    Pieper, Korbinian; Schuster, Tibor; Levionnois, Olivier; Matis, Ulrike; Bergadano, Alessandra

    2011-03-01

    To assess the antinociceptive efficacy of transdermal (TD) buprenorphine (B) in dogs, a prospective, positive-controlled experimental study was performed in 10 healthy Beagles. In an open label crossover design, the dogs initially received intravenous B (IVB, 0.02 mg kg(-1)) as a positive control, followed by TDB (52.5 μg h(-1)) 4 months later. Blood was collected at regular intervals for determination of the plasma concentrations of B ([B]) and its metabolite norbuprenorphine. The antinociceptive efficacy was assessed using thermal and mechanical models of nociception. The peak concentration [B] was 1.54 ng mL(-1) (±1.98) 60 h after TDB application, although three dogs had no measurable [B] after TDB. Maximum thermal threshold (TT) was 52.6 °C (±0.48) at 1h after IVB administration and 51.63 °C (±1.01) 72 h after TDB application. The significant increase in TT indicated that effective antinociception was achieved beyond 36 h after the application of TDB, lasting until patch removal. There was hysteresis between [B] and the antinociceptive effect. PMID:20206560

  7. Fentanyls: Are we missing the signs? Highly potent and on the rise in Europe.

    PubMed

    Mounteney, Jane; Giraudon, Isabelle; Denissov, Gleb; Griffiths, Paul

    2015-07-01

    Fentanyl is a synthetic opioid analgesic historically used as a pain reliever and an anaesthetic. Recent concerns have arisen around the illicit use of fentanyl and its analogues in a number of European countries, linked to their high potency and associated risk of fatal overdose. Evidence has been emerging from Estonia for over a decade of entrenched patterns of fentanyl use, including injection of the drug and hundreds of overdose deaths. More recently, reports indicate that both fentanyl and 3-methylfentanyl (TMF) have been marketed as a replacement for heroin in European countries (e.g. Bulgaria, Slovakia) affected by heroin shortages. In addition, Germany, Finland and the United Kingdom, reported new outbreaks of fentanyl-related deaths. This combination of increasing mortality data alongside law enforcement intelligence suggesting both diversion and illicit production of fentanyls, prompted wider investigation using a targeted multi-source data collection exercise and analysis. This identified that in the European context, fentanyls are 'low use but high risk/harm' substances. Evidence shows that Estonia stands out as having an endemic problem, while the use of fentanyls in other European countries appears to be geographically localised. Developments in illicit supply of fentanyls reflect the complexity of Europe's contemporary drug market: manifesting illicit production and use, the diversion and misuse of medicines, and the online sale of non-controlled new psychoactive substances. Likewise effective and integrated responses will need to address fentanyl production, diversion as well as ensuring the availability of harm reduction measures to users. PMID:25976511

  8. Radioreceptor assay for analysis of fentanyl and its analogs in biological samples

    SciTech Connect

    Alburges, M.E.

    1988-01-01

    The assay is based on the competition of these drugs with ({sup 3}H) fentanyl for opioid receptors in membrane preparations of rat forebrain in vitro. The binding in stereospecific, reversible and saturable. Scatchard plots of saturation suggest the presence of high and low affinity binding sites. Morphine and hydromorphone complete with ({sup 3}H)fentanyl for the opioid receptor, but other morphine-like compounds were relatively weak displacers of ({sup 3}H)fentanyl. Many other commonly abused drugs do not compete with ({sup 3}H)fentanyl for the opioid receptors. Urine samples from animals injected with fentanyl, ({plus minus})-cis-3-methylfentanyl, alpha-methylfentanyl, butyrylfentanyl and benzylfentanyl were analyzed by radioreceptor assay, radioimmunoassay, and gas chromatography/mass spectrometry. Urinary analysis of fentanyl showed a good correlation with these three methods; however, discrepancies were observed in the analysis of fentanyl analogs. This radioreceptor assay is well-suited as an initial assay for the detection of active analogs of fentanyl in urine with good correlation with other techniques in the analysis of fentanyl; however, there is substantial disagreement between techniques in the quantitation of fentanyl analogs. The implications of these discrepancies are discussed.

  9. Challenges and opportunities in dermal/transdermal delivery

    PubMed Central

    Paudel, Kalpana S; Milewski, Mikolaj; Swadley, Courtney L; Brogden, Nicole K; Ghosh, Priyanka; Stinchcomb, Audra L

    2010-01-01

    Transdermal drug delivery is an exciting and challenging area. There are numerous transdermal delivery systems currently available on the market. However, the transdermal market still remains limited to a narrow range of drugs. Further advances in transdermal delivery depend on the ability to overcome the challenges faced regarding the permeation and skin irritation of the drug molecules. Emergence of novel techniques for skin permeation enhancement and development of methods to lessen skin irritation would widen the transdermal market for hydrophilic compounds, macromolecules and conventional drugs for new therapeutic indications. As evident from the ongoing clinical trials of a wide variety of drugs for various clinical conditions, there is a great future for transdermal delivery of drugs. PMID:21132122

  10. Sperm Patch-Clamp

    PubMed Central

    Lishko, Polina; Clapham, David E.; Navarro, Betsy; Kirichok, Yuriy

    2014-01-01

    Sperm intracellular pH and calcium concentration ([Ca2+]i) are two central factors that control sperm activity within the female reproductive tract. As such, the ion channels of the sperm plasma membrane that alter intracellular sperm [Ca2+] and pH play important roles in sperm physiology and the process of fertilization. Indeed, sperm ion channels regulate sperm motility, control sperm chemotaxis toward the egg in some species, and may trigger the acrosome reaction. Until recently, our understanding of these important molecules was rudimentary due to the inability to patch-clamp spermatozoa and directly record the activity of these ion channels under voltage clamp. Recently, we overcame this technical barrier and developed a method for reproducible application of the patch-clamp technique to mouse and human spermatozoa. This chapter covers important aspects of application of the patch-clamp technique to spermatozoa, such as selection of the electrophysiological equipment, isolation of spermatozoa for patch-clamp experiments, formation of the gigaohm seal with spermatozoa, and transition into the whole-cell mode of recording. We also discuss potential pitfalls in application of the patch-clamp technique to flagellar ion channels. PMID:23522465