Selegiline Research Articles

Box–Behnken experimental design for preparation and optimization of the intranasal gels of selegiline hydrochloride

Selegiline hydrochloride (SL) is chosen as an adjunct for the control of clinical signs of Parkinsonian patients. The aim of the present work is to develop and optimize thermosensitive gels using Pluronic (F-127) for enhancing transport of SL into the brain through the nasal route. SL gels were prepared using a cold method and the Box–Behnken experimental design methodology. Drug (SL), gelling agent (F-127), and emulsifier (Propylene glycol, PG) were selected as independent variables, while the gelation temperature, gel strength, pH, gel content, and gel erosion were considered as dependent variables. For further understanding of the interaction between the various variables, contour plots and surface plots were also applied. Selected formulations, like S10 (contain 25 mg SL, 20 g F-127, and 1 g PG) and S14 (contain 50 mg SL, 18 g F-127 and 1 g PG), had a clear appearance in the sol form, with gelling temperature of the nasal gel ranging between 33 and 34, respectively. The gel strength of the formulations varied from 4.67 and 0.68 mm and the drug content was 100%. The pH of the formulations ranged between 6.71 and 7.11. Detachment force was acceptable (63.69–244.16 N/cm2) to provide prolonged adhesion. In vitro, drug release studies showed that the prepared formulations could release SL for up to 8 h. Permeation flux for the S10 gel was 0.0002 mg/min/cm2. Results demonstrated that the potential use of SL gels can enhance the therapeutic effect of SL through the intranasal administration.

Effects of Antiparkinson Medication on Cognition in Parkinson's Disease: A Systematic Review.

This study aimed to systematically review the effects of currently prescribed antiparkinson medication on cognition in patients with mild-to-moderate Parkinson's disease (PD) who were either cognitively intact or mildly impaired. English- and French-language studies published between 1969 and 2017 were accessed via MedLine, PsychNET, EMBASE and EBSCO databases. Methodological quality (MQ) was evaluated with the quality assessment instrument of the Cochrane Collaboration Depression, Anxiety and Neurosis Review (scores from 0% to 44% indicate very low quality; scores from 45% to 64% indicate low quality; scores from 65% to 84% indicate medium quality; and scores from 85% to 100% indicate high quality). Hedges' g and Student's t-test were performed on all cognitive outcome measures reported. In total, 14 studies assessed the cognitive effects of levodopa (L-D), pramipexole (PRX), selegiline (SEL) and rasagiline (RAS) in mild-to-moderate non-demented PD patients. The MQ was overall low, with an average score of 49.1%. Results for L-D showed deleterious effects on a test of cognitive inhibition, as well as benefits on tests of attention/processing speed/working memory, executive functions and episodic memory. Pramipexole was associated with a worsening of episodic memory and impulse control. Results on SEL indicated a deterioration of global cognition over time and of concept formation. Rasagiline had some benefits on working memory and verbal fluency. Antiparkinson medications can have deleterious (L-D; PRX; SEL) and beneficial (L-D; RAS) effects on cognition. However, randomized double-blind placebo-controlled trials with larger sample sizes are required to better elucidate this issue.

Preparation and In Vitro/Ex Vivo Evaluation of Buccoadhesive Discs of an Anti-Parkinson Drug: Relationship between Mucoadhesivity, Drug Release and Permeability

Background: Selegiline hydrochloride (Sel) is a drug applied for the therapy of early‐step Parkinson's disease. In usual clinical doses, it is an elective irreversible MAO-B inhibitor. This study intended to formulate mucoadhesive microspheres of selegiline with the objective of improving the therapeutic efficacy, patient compliance and bioavailability. Methods: The microspheres were prepared by emulsion solvent evaporation method (O1/ O2) using hydroxypropyl methylcellulose (HPMC). In the current study, bucco‐adhesive microspheres were prepared with different drug to polymer ratios and characterized by encapsulation efficiency, particle size, Differential Scanning Calorimetry (DSC), FTIR Fourier Transform Infrared Spectroscopy (FTIR), flowability, the degree of swelling and surface pH, mucoadhesive character, retentive time, and drug release studies. Results: The best drug to polymer ratio in microspheres was 1:2 (as F1). The production yield microspheres F1 showed production yield of 84.79%, mean particle size of 744.73 μm and loading efficiency of 53.33%. The DSC exhibited the property of selegiline loaded microspheres changed to amorphous form. The FTIR spectrum proposed that the drug kept its chemical stability during the emulsification process. The results showed that the microspheres of F1 had faster release than the microspheres of F2 (1:4), F3 (1:6), and commercial tablet (p<0.05). The microspheres did not exhibit good retention time properties (276.66‐329.66 min). The results of mucoadhesion strength (8.3‐18.3 g/cm2) and surface pH of discs (6.44‐6.97) showed the better characterization of microspheres in buccal. Conclusion: The formulations were found to be appropriate candidates for the improvement of microspheres for the remedial objects.

Long-term Monitoring Gait Analysis Using a Wearable Device in Daily Lives of Patients with Parkinson's Disease: The Efficacy of Selegiline Hydrochloride for Gait Disturbance.

The aim of this study was to assess quantitatively the gait disorders in the daily lives of patients with Parkinson's disease (PD) using with a newly developed portable gait rhythmogram (PGR), which has a trunk-mounted acceleration sensor and automatic gait-detection algorithm. Using the PGR, we recorded the daily walking profiles of 14 PD patients before and after the addition or increase in dose of an MAO-B inhibitor (selegiline, average dose: 4.0 mg/day) as part of their medicine regimen, and evaluated their gait using the unified Parkinson's disease rating scale (UPDRS) and scores from a freezing of gait (FOG) questionnaire. Before treatment with selegiline, the overall movements per 24 h was decreased below 0.41 m/s2 (mean - 1.5 SD) in eight patients. The mean gait acceleration was decreased below 1.94 m/s2 (mean - 2 SD) in 10 patients. The slope of the linear regression line was increased to 1.6 (mean + 1.5 SD) in eight patients. The cadence was increased to 124 steps/min (mean + 1.5 SD) in four patients. Based on continuous PGR recordings in the daily lives of the patients for 24 h, the addition or increase in dose of selegiline increased the amplitudes of gait accelerations in 4 of 10 patients (40.0%), widened the range of gait accelerations in 5 of 8 patients (62.5%), diminished the cadence in 4 of 4 patients (100%), and diminished the fluctuations in gait throughout the day in 12 of 14 patients (85.7%). The UPDRS III and FOG scores significantly improved after the addition or increase in dose of selegiline (p < 0.005, p < 0.01, respectively). However, changes in gait-related scores of UPDRS were not detected in six patients. Improvements in the gait fluctuations of PD patients after the addition or increase in dose of selegiline were detected using the PGR in the daily lives of the patients for 24 h. The PGR had a higher sensitivity for detecting the improvements than UPDRS scores.

Selegiline hydrochloride (SEL) inhibits the uptake of 3 meta–iodobenzylguanidine (MIBG) and influences the result of MIBG myocardial scintigraphy in patients with parkinsonism

Selegiline hydrochloride (SEL) inhibits the uptake of 3 meta–iodobenzylguanidine (MIBG) and influences the result of MIBG myocardial scintigraphy in patients with parkinsonism

The relation between isatin and selegiline by the alteration of serum isatin, an endogenous monoamine oxidase inhibitor, induced by selegiline hydrochloride in Parkinson's disease

Background: Monoamine oxidase (MAO) is an enzyme that metabolizes a wide range of monoamines and play an important role in the control of neurotransmitter concentrations. However, the detailed CNS functions of an endogenous MAO inhibitor, isatin, were not determined. Isatin was found to be a potent MAO inhibitor that is more active against MAO-B than MAO-A. Exogenously administered isatin increased dopamine (DA) levels in the rat striatum. Furthermore isatin improves motor dysfunction and the DA levels in the striatum in rat model of Parkinson’s disease(Ogata et al., 2003). We showed the low concentration in the serum isatin was found in Parkinson's disease patients as compared with controls.

Appraisal of Transdermal Water-in-Oil Nanoemulgel of Selegiline HCl for the Effective Management of Parkinson's Disease: Pharmacodynamic, Pharmacokinetic, and Biochemical Investigations.

In the present study, the potential of transdermal nanoemulsion gel of selegiline hydrochloride for the treatment of Parkinson's disease was investigated. Water-in-oil nanoemulsions were developed by comparing low- and high-energy methods and were subjected to thermodynamic stability tests, in vitro permeation, and characterization studies. In vitro studies indicated that components of nanoemulsion acted as permeation enhancers with highest flux of 3.531±1.94μg/cm2/h from nanoemulsion SB6 containing 0.5mg selegiline hydrochloride, 3% distilled water, 21% S mix (Span 85, Tween 80, PEG 400), and 76% isopropyl myristate by weight. SB6 with the least droplet size of 183.4±0.35nm, polydispersity index of 0.42±0.06 with pH of 5.9±0.32 and viscosity of 22.42±0.14cps was converted to nanoemulsion gel NEGS4 (viscosity=22,200±400cps) by addition of Viscup160® for ease of application and evaluated for permeation, safety, and pharmacokinetic profile in Wistar rats. It provided enhancement ratio 3.69 times greater than conventional gel. NEGS4 showed 6.56 and 5.53 times increase in bioavailability in comparison to tablet and conventional gel, respectively, along with sustained effect. Therefore, the developed water-in-oil nanoemulsion gel promises to be an effective vehicle for transdermal delivery of selegiline hydrochloride.

Effectiveness of spinal cord stimulation for painful camptocormia with Pisa syndrome in Parkinson\u2019s disease: a case report

BackgroundSpinal cord stimulation (SCS) has recently been reported to be effective for truncal postural abnormalities such as camptocormia and Pisa syndrome in Parkinson’s disease. In this case report, we describe a case of a woman with Parkinson’s disease in whom SCS was effective for painful camptocormia with Pisa syndrome.Case presentationA 65-year-old woman was admitted to our hospital because of painful camptocormia. She had noticed resting tremor in the left upper limb and aprosody at 48 years of age. She was diagnosed as having Parkinson’s disease (Hoehn & Yahr stage 1) at 53 years of age. Cabergoline was started during that same year, with subsequent addition of selegiline hydrochloride; the symptoms of parkinsonism disappeared. Wearing-off occurred when she was 57 years old, 3 years after starting carbidopa/levodopa, and truncal postural abnormalities—painful camptocormia with Pisa syndrome to the right—appeared at 58 years of age. These symptoms worsened despite adjustment of her oral medications, and deep brain stimulation (DBS) was performed when she was 60 years old. The truncal postural abnormalities improved after DBS, and she could travel abroad at 61 years of age. However, from 62 years of age, painful camptocormia with Pisa syndrome to the right reappeared. The pain was unsuccessfully treated with oral analgesics, radiofrequency coagulation of the dorsal and medial branches of the lumbar spinal nerve, and lumbar epidural block. Finally, SCS was performed for the pain relief. The pain disappeared immediately after SCS and her posture then gradually improved. Unified Parkinson’s Disease Rating Scale score improved from 48 to 34 points and Timed Up and Go Test improved from 15 s to 7 s after SCS.ConclusionsThis case suggests that SCS may be effective for improving painful truncal postural abnormalities and motor complications of Parkinson’s disease. Pain relief or a direct effect on the central nervous system by SCS was considered to explain the alleviation of these symptoms.

Brain targeted delivery of mucoadhesive thermosensitive nasal gel of selegiline hydrochloride for treatment of Parkinson's disease

Selegiline hydrochloride (SL), is an anti-Parkinson’s agent, has low-oral bioavailability due to its high first pass metabolism and scarce oral absorption. In the present study, SL mucoadhesive nasal thermosensitive gel (SNT-gel) was prepared to enhance the bioavailability and subsequently, its concentration in the brain. The SNT-gel was prepared using Poloxamer 407-Chitosan combination and optimised formulation was further evaluated for physicochemical parameters. The comparative pharmacodynamic studies including behavioural studies, biochemical testing and histopathology of the brain was carried out in rats for SNT-gel, SL-nasal solution and SL Marketed Tablets. The optimised SNT-gel formulation (SNT-V) revealed sol-gel transition at 33–34°C. In-vitro diffusion study of SNT-V showed 102.37 ± 2.1% diffusion at 12 h which reduced to 89.64 ± 1.2% in Ex-vivo diffusion. Comparative results of behavioural studies indicated an improved score of photoactometer and reduced motor deficit (catalepsy score) in SNT-gel treatment group as compared with other groups. Similarly, a significant increase in brain dopamine, reduction in monoamine oxidase B level, increase in catalase activity and level of reduced glutathione upon treatment with SNT-gel indicated its effectiveness which was also supported by histopathology results. Therefore, nasal thermosensitive gel holds better potential for brain targeting in Parkinson’s disease over the conventional nasal or oral formulations.

Biosensor for the characterisation of hMAO B inhibitors and the quantification of selegiline

A novel human monoamine oxidase B (hMAO B) based biosensor for inhibitory measurements was developed. It allows both the characterisation of the type of enzyme inhibition and the sensitive and simple determination of inhibitors like selegiline hydrochloride. The sensor consists of a screen printed carbon working electrode modified with 20% manganese dioxide (MnO2) and the enzyme hMAO B, which was immobilised on the electrode via a dialysis membrane (regenerated cellulose, molecular weight cut-off 14000). Inhibition of hMAO B is evaluated by adding different concentrations of the inhibitor selegiline hydrochloride to the enzyme and applying a defined amount of the hMAO B substrate phenylethylamine (PEA). The enzymatically formed H2O2 is amperometrically detected at 0.4V vs. Ag/AgCl in a flow injection analysis (FIA) system. With 100µM PEA the sensor showed a linear correlation between peak height and inhibitor concentration in a range of 0.51–3.25µg/mL selegiline hydrochloride. LOD and LOQ were determined to be 0.15 and 0.51µg/mL, respectively. The sensor showed a repeatability of 3.7% and an intermediate precision of 8.1%. The inhibition-based biosensor was successfully employed to quantify selegiline hydrochloride in pharmaceutical samples. Kinetic studies via Lineweaver-Burk plot and enzyme quantity vs. current plot revealed that the inhibition is irreversible.

Development and in vitro evaluation of potential electromodulated transdermal drug delivery systems based on carbon nanotube buckypapers

Buckypapers based on different types of carbon nanotubes with and without the addition of four model drugs, two of basic nature (clonidine hydrochloride, selegiline hydrochloride) and the others of acidic character (flurbiprofen, ketorolac tromethamine) were prepared and characterized. The influence of the conditions employed in the preparation of the buckypapers (dispersion time and solvents used in the preparation, as well as the type of carbon nanotubes used and the characteristics of the drug involved) on their conductivity was especially examined. The in vitro performance of the drug loaded buckypapers as passive and active transdermal drug release systems, the latter being modulated by means of the application of electric voltages, was studied. Passive drug loaded buckypapers presented characteristic release profiles, also depending on the drug used, which indicate differences in the drug-carbon nanotubes non-covalent interactions. Application of electrical biases of appropriate polarities enabled the modulation of the drug release profiles in any desired direction. Different mathematical models were fitted to passive and electromodulated experimental release data for the four model drugs. Among these models, the most appropriate for data description was a two-compartment pseudo-second-order one.

Effect of Oleracein E, a Neuroprotective Tetrahydroisoquinoline, on Rotenone-Induced Parkinson's Disease Cell and Animal Models.

Oleracein E (OE), a tetrahydroisoquinoline possessing potent antioxidant activity, was first isolated from a traditional Chinese medicine, Portulaca oleraea L., and is hypothesized to be a neuroprotectant. In the present study, we evaluated the effects of racemic OE on rotenone-induced toxicity in Parkinson's disease (PD) cell and animal models. Pretreatment with OE (10 μM, 2 h) decreased lactic acid dehydrogenase (LDH) release and the apoptosis rate in rotenone (5 μM, 24 h)-treated SH-SY5Y human neuroblastoma cells. Further mechanistic study indicated that OE reduced reactive oxygen species (ROS) levels, inhibited extracellular signal-regulated kinase (ERK) 1/2 phosphorylation, reduced rotenone-induced up-regulation of the proapoptotic protein Bax, and prevented cytochrome C release and caspase-3 activation. In a rotenone-treated (intragastric 30 mg/(kg·d), 56 d) C57BL-6J mouse model, OE (intragastric 15 mg/(kg·d), 56 d) improved motor function, as indicated by an increased moving distance in the spontaneous activity test and sustained time on the rota-rod test. OE also elevated superoxide dismutase (SOD) activity, decreased malonaldehyde content, and reduced ERK1/2 phosphorylation in the midbrain and striatum of mice treated with rotenone. Furthermore, OE preserved tyrosine hydroxylase-positive neurons and maintained the density of dopaminergic (DAergic) fibers in the substantia nigra pars compacta (SNpc). Some of the effects of OE on PD models were similar to those of the positive control selegiline hydrochloride. Our results demonstrated that OE protects DAergic neurons against rotenone toxicity through reducing oxidative stress and down-regulating stress-related molecules. OE is worth exploring further for its neuroprotectant properties in the prevention and treatment of PD.

A novel and simple electrochemical sensor for some dopaminergic drugs such as selegiline and pramipexole based on a nickel nanoparticle modified carbon paste electrode

In this work, the electrocatalytic oxidation of some dopaminergic drugs such as selegiline (SEL) and pramipexole (PX) was carried out, for the first time with a nickel nanoparticle modified carbon paste electrode (Ni-NP/MCPE).

Comparison of two methods for selegiline determination: A flow-injection chemiluminescence method using cadmium sulfide quantum dots and corona discharge ion mobility spectrometry

Two analytical approaches including chemiluminescence (CL) and corona discharge ionization ion mobility spectrometry (CD-IMS) were developed for sensitive determination of selegiline (SG). We found that the CL intensity of the KMnO4–Na2S2O3 CL system was significantly enhanced in the presence of l-cysteine capped CdS quantum dots (QDs). A possible CL mechanism for this CL reaction is proposed. In the presence of SG, the enhanced CL system was inhibited. Based on this inhibition, a simple and sensitive flow-injection CL method was proposed for the determination of SG. Under optimum experimental conditions, the decreased CL intensity was proportional to SG concentration in the range of 0.01 to 30.0mgL−1. The detection limit (3σ) was 0.004mgL−1. Also, SG was determined using CD-IMS, and under optimum conditions of CD-IMS, calibration curves were linear in the range of 0.15 to 42.0mgL−1, with a detection limit (3σ) of 0.03mgL−1. The precision of the two methods was calculated by analyzing samples containing 5.0mgL−1 of SG (n=11). The relative standard deviations (RSDs%) of the flow-injection CL and CD-IMS methods are 2.17% and 3.83%, respectively. The proposed CL system exhibits a higher sensitivity and precision than the CD-IMS method for the determination of SG.

Pharmacological evaluation of nasal delivery of selegiline hydrochloride-loaded thiolated chitosan nanoparticles for the treatment of depression

The aim of the present study was to investigate the propensity of thiolated chitosan nanoparticles (TCNs) to enhance the nasal delivery of selegiline hydrochloride. TCNs were synthesized by the ionic gelation method. The particle size distribution (PDI), entrapment efficiency (EE), and zeta potential of modified chitosan (CS) nanoparticles were found to be 215 ± 34.71 nm, 70 ± 2.71%, and + 17.06 mV, respectively. The forced swim and the tail suspension tests were used to evaluate the anti-depressant activity, in which elevated immobility time was found to reduce on treatment. TCNs seem to be promising candidates for nose-to-brain delivery in the evaluation of antidepressant activity.

Spectrophotometric determination of selegiline hydrochloride in bulk and in pharmaceutical formulations

Spectrophotometric determination of selegiline hydrochloride in bulk and in pharmaceutical formulations

Fabrication and in vitro characterization of polymeric nanoparticles for Parkinson's therapy: a novel approach

The objective of the research was to formulate and evaluate selegiline hydrochloride loaded chitosan nanoparticles for the Parkinson's therapy in order to improve its therapeutic effect and reducing dosing frequency. Taguchi method of design of experiments (L9 orthogonal array) was used to get optimized formulation. The selegiline hydrochloride loaded chitosan nanoparticles (SHPs) were prepared by ionic gelation of chitosan with tripolyphosphate anions (TPP) and tween 80 as surfactant. The SHPs had a mean size of (303.39 ± 2.01) nm, a zeta potential of +32.50mV, and entrapment efficiency of SHPs was 86.200 ± 1.38%. The in vitro drug release of SHPs was evaluated in phosphate buffer saline (pH 5.5) using goat nasal mucosa and found to be 82.529% ± 1.308 up to 28 h. Release kinetics studies showed that the release of drug from nanoparticles was anomalous (non-fickian) diffusion indicating the drug release is controlled by more than one process i.e. superposition of both phenomenon, the diffusion controlled as well as swelling controlled release. SHPs showed good stability results as found during stability studies at different temperatures as mentioned in ICH guidelines. The results revealed that selegiline hydrochloride loaded chitosan nanoparticles are most suitable mode of delivery of drug for promising therapeutic action.

Novel Spectrophotometric Methods for the Determination of Selegiline Hydrochloride in Bulk and Its Pharmaceutical Preparation

A simple and highly selective spectrophotometric method has been developed for the determination of selegiline hydrochloride in bulk and formulations. Method A is based on the oxidation of 3-methyl-2-benzothiazolinone hydrazone in the presence of ceric ammonium sulphate, followed by its coupling reaction with drug to form a colored product having λmax of 629 nm. Method B is based on the coupling reaction of drug with 4-aminoantipyrine to give a new ligand that reacts with copper(II) to give intense bluish red colored chelate which is measured at 539 nm. Beer’s law is obeyed in the range of 10.00–85.00 μg mL−1 with molar absorptivity of 0.98×104 for method A and 20.00–120.00 μg mL−1 with molar absorptivity of 0.94×104 for method B. The optimum reaction condition and the analytical parameters are evaluated. The results obtained indicate that the methods are free from interference of the ingredients; thus they are successfully applied to pharmaceutical formulations.

Development and evaluation of buccoadhesive tablet for selegiline hydrochloride based on thiolated polycarbophil

Selegiline hydrochloride (SHCl), a monoamine oxidase B inhibitor, is used as an adjunct in the therapy of Parkinson’s disease. This study is concerned with the preparation and evaluation of mucoadhesive buccal tablet for controlled systemic delivery of SHCl. Buccal absorption of selegiline can bypass its first-pass metabolism and improve bioavailability accompanied by greatly reduced metabolite formation, which is potentially of enhanced therapeutic value in patients with Parkinson’s disease. Polycarbophil–cysteine (PCP–cys) conjugate, which is a thiolated derivative of the mucoadhesive polymer polycarbophil, was synthesized by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride-mediated amide bond coupling. Tablets of SHCl based on native and thiolated polycarbophil were prepared. The prepared tablets were evaluated for drug content, swelling behavior, mucoadhesive strength, in vitro drug release, ex vivo permeation and in vitro cytotoxicity. PCP–cys tablets showed enhanced mucoadhesion and retarded drug release compared to polycarbophil tablets. Permeation data of SHCl from matrices prepared using the PCP–cys polymer revealed a significantly higher value of apparent permeability in comparison to polycarbophil, which supported the information in literature that thiolation imparts permeation enhancing properties to mucoadhesive polymers. In vitro cytotoxicity studies on PCP–cys using L-929 mouse fibroblast cell line indicated that conjugation with cysteine does not impart any apparent toxicity to polycarbophil. The results from the study indicate that the buccal delivery of SHCl using thiolated polycarbophil tablet could provide a way for improved therapy of Parkinson’s disease.

Design, Development and Evaluation of Selegiline Hydrochloride Transdermal Patch

Many monoamine oxidase inhibitors (MAOIs) have been used to treat major depressive disorder (MDD). However, the prescription of MAOIs has decreased considerably as a result of side effects such as tyramine-induced hypertensive crisis, known as “Cheese Effect”. The drug delivery system itself can affect the effi cacy and bioavailability of certain drugs when medications are given by oral, intravesical and intravaginal routes. Therefore there is a need for advanced drug delivery techniques that can avoid toxic effects and improve the bioavailability at the same time. In this context, the transdermal patches of selegiline hydrochloride (SH) were prepared by the solvent casting method using hydroxy propyl methyl cellulose (HPMC), polyvinyl alcohol (PVA) and methyl cellulose (MC) as reservoir polymers in different ratios (1:1, 1:2 and 1:3). Rate controlling membrane was caste by using 2% ethyl cellulose (EC) membrane. The prepared patches possessed satisfactory physicochemical characteristics. The formulation exhibited fl exibility, uniform weight, thickness, smoothness, drug content (93 to 97 %), little moisture loss and moisture absorption. The in-vitro permeation studies in phosphate buffer (pH 7.4) revealed formulations released drug in the range of 86.77 to 96.79% and followed diffusion mechanism. Formulations with 1:1 and 1:2 ratio released drug up to 10 to 20 h only. The optimized formulation F6 containing PVA (1:3) showed good release rate of 90.08% for 24 h. The patches were seemingly free of potential hazardous skin irritation. FT-IR and DSC studies revealed no interaction between the drug and polymers used.