Matrix Type Transdermal Drug Delivery Research Articles

Formulation and evaluation of transdermal patch of carbamazepine

Transdermal drug delivery system (TDDS) is a widely accepted mode of drug delivery method due to various advantages and one of the novel routes for systemic delivery of drugs through intact skin. Topical drug administration is a systemic and localized method of delivering drugs through skin and is considered an attractive alternative to oral and parenteral routes. The aim of present study was to formulate and evaluate Matrix type transdermal drug delivery system (TDDS) of Carbamazepine was prepared by the solvent evaporation technique. Several batches were prepared by using combination of HPMC E-15, Eudragit RL-100, and Ethyl Cellulose different ratios. Propylene glycol was used as plasticizer and DMSO was incorporated as a permeation enhancer. These Formulated transdermal patches were characterized for their physicochemical parameters like thickness, weight variation, folding endurance, percentage moisture uptake, Percentage moisture uptake and In vitro drug release studies were examined. Among the above all formulation F6 was chosen as a best Formulation, because this optimised formulation showed satisfactory drug content, physical characteristic for its thickness, weight uniformity, percentage moisture content, percentage moisture uptake, and maximum % of drug release i.e., 93.95 % in 12 hours. The optimized formulation (F6) showed maximum highest percentage of drug release.

Development and evaluation of buspirone hyrdochloride loaded transdermal patch using natural polymers

The purpose of this present study was to design and develop a Buspirone hydrochloride loaded matrix type transdermal drug delivery system (TDDS) with four natural gum polymers such as Guar gum, Gellan gum, Xanthan gum, Karaya gum. A total of twelve batch of matrix patches were formulated with above stated polymers and other excipient like Glycerin, Propylene glycol (PG), Polyethylene glycol (PEG) as plasticizer. These all batches were characterized by evaluation parameters which including drug content, flatness, thickness, uniformity of weight, folding endurance, moisture content, moisture uptake and to determine the amount of Buspirone hydrochloride present in the matrix of patches in vitro dissolution study of all twelve formulations were performed. Fourier transform infrared (FTIR) technique and Differential Scanning Colorimetry (DSC) carried out to determine interaction between Buspirone HCl and excipients which are present in patch. Permeation study of patch of Buspirone HCl was performed in Franz's diffusion cell to evaluate In-vitro skin permeation and it was found that batch G3 shows 98.89% permeability. After evaluating all batches and based on results which are obtained characterization and In-Vitro dissolution it was concluded that patches containing natural polymers are not showing any interaction and better release study.

FORMULATION AND EVALUATION OF CLOPIDOGREL BISULFATE TRANSDERMAL PATCHES

Transdermal drug delivery is an alternative route for systemic drug delivery which minimizes the absorption and increases the bioavailability. The main objective of the present work was to develop a suitable matrix type transdermal drug delivery system of Clopidogrel bisulphate using different polymers HPMC E15, Eudragit L100 and to compare the drug release through physical method and chemical method. Matrix type transdermal patches containing Clopidogrel Bisulfate were prepared by solvent evaporation technique. The prepared transdermal patches were evaluated for Thickness, folding endurance, tensile strength and in vitro studies. The prepared transdermal drug delivery system of Clopidogrel bisulphate using different polymers such as HPMC E15 and Eudragit L 100 had shown good promising results for all the evaluated parameters. Based on the In-vitro drug release, drug content and folding endurance results formulation F4 was concluded as an optimized formulation which shows its higher percentage of drug release.
 Keywords: Transdermal drug delivery, Clopidogrel bisulphate, HPMC E15, Eudragit L100

Fabrication and characterization of matrix type transdermal patches loaded with tizanidine hydrochloride: potential sustained release delivery system

Objective: This study was designed to optimize and develop matrix type transdermal drug delivery system (TDDS) containing tizanidine hydrochloride (TZH) using different polymers by solvent evaporation method.Significance: A strong need exists for the development of transdermal patch having improved bioavailability at the site of action with fewer side effects at off-target organs.Methods: The patches were physically characterized by texture analysis (color, flexibility, smoothness, transparency, and homogeneity), in vitro dissolution test and FTIR analysis. Furthermore, functional properties essential for TDDS, in vitro percentage of moisture content, percentage of water uptake, in vitro permeation by following different kinetic models, in vivo drug content estimation and skin irritation were determined using rabbit skin.Results: The optimized patches were soft, of uniform texture and thickness as well as pliable in nature. Novel transdermal patch showed ideal characteristics in terms of moisture content and water uptake. FTIR analysis confirmed no interaction between TZH and cellulose acetate phthalate (CAP). The patch showed sustained release of the drug which increased the availability of short acting TZH at the site of action. The patch also showed its biocompatibility to the in vivo model of rabbit skin.Conclusions: The results demonstrated that topically applied transdermal patch will be a potential medicated sustain release patch for muscle pain which will improve patient compliance.

DEVELOPMENT AND IN-VITRO EVALUATION OF MATRIX-TYPE TRANSDERMAL PATCHES OF LOSARTAN POTASSIUM

Objective: Since last decade drugs through skin has received great attention of many researchers. The aim of present study was designed to develop a suitable matrix type transdermal drug delivery system (TDDS) of Losartan potassium. Methods: Four transdermal patches formulations of Losartan potassium were prepared by using different polymers using blends of different polymers like polyvinylpyrrolidone K30 (PVP K30) and ethylcellulose (EC), hydroxypropyl methyl cellulose and chitosan. Physical studies including thickness, folding endurance moisture content, tensile strength and flatness were performed on all formulations. In-vitro diffusion study of 10 hrs was performed by means of Franz diffusion cell. Results: Thickness of four prepared patches lies in the range of 0.30 to 0.33 mm. Percent moisture content was found to be in the range of 2.56 to 3.44. The cumulative percent drug release after 10 hrs in between 38.41 to 80.41%. Stability study performed on selective batch, TP1 for 12 weeks at different temperature indicates stability of transdermal patches at room temperature. Conclusion:Present study concluded that Losartan potassium can be formulated into the transdermal matrix type patches to sustain its release characteristics. Polymeric composition of batch TP1 (PVP K30: Chitosan: 70:30) was found to be the best choice for manufacturing transdermal patches of Losartan potassium among the formulations studied. Peer Review History: Received 2 April 2017; Revised 12 May; Accepted 13 May, Available online 15 May 2017 UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file: Reviewer's Comments: Average Peer review marks at initial stage: 5.5/10 Average Peer review marks at publication stage: 8.0/10 Reviewer(s) detail: Asmaa Ahmed Mohamed Ahmed Khalifa, Pharos University, Alexandria, Egypt, asmaa.khalifa@pua.edu.eg Dr. Dalia Kamal Zaffar Ali, Modern University for technology and information, Egypt, dr.moda88@gmail.com Similar Articles: DEVELOPMENT AND EVALUATION OF MATRIX TYPE TRANSDERMAL PATCHES OF PIOGLITAZONE HYDROCHLORIDE

Preparation and characterization of metoprolol tartrate containing matrix type transdermal drug delivery system.

The present study aimed to develop matrix-type transdermal drug delivery system (TDDS) of metoprolol tartrate using polyvinyl pyrrolidone (PVP) and polyvinyl alcohol (PVA). The transdermal films were evaluated for physical parameters, Fourier transform infrared spectroscopy analysis (FTIR), differential scanning calorimetry (DSC), in vitro drug release, in vitro skin permeability, skin irritation test and stability studies. The films were found to be tough, non-sticky, easily moldable and possess good tensile strength. As the concentration of PVA was increased, the tensile strength of the films was also increased. Results of FTIR spectroscopy and DSC revealed the absence of any drug-polymer interactions. In vitro release of metoprolol followed zero-order kinetics and the mechanism of release was found to be diffusion rate controlled. In vitro release studies of metoprolol using Keshary-Chein (vertical diffusion cell) indicated 65.5% drug was released in 24h. In vitro skin permeation of metoprolol transdermal films showed 58.13% of the drug was released after 24h. In vitro skin permeation of metoprolol followed zero-order kinetics in selected formulations. The mechanism of release was found to be diffusion rate controlled. In a 22-day skin irritation test, tested formulation of transdermal films did not exhibit any allergic reactions, inflammation, or contact dermatitis. The transdermal films showed good stability in the 180-day stability study. It can be concluded that the TDDS of MPT can help in bypassing the first-pass effect and will provide patient improved compliance, without sacrificing the therapeutic advantages of the drugs.

Matrix type transdermal patches of captopril: Ex vivo permeation studies through excised rat skin

Background/objectivesCaptopril, "an ACE inhibitor" has comparatively short elimination half life and its oxidation rate in dermal homogenate is significantly lower than that in intestinal homogenate. So as to enhance the bioavailability and to reduce the difficulties associated with captopril, it is decided to design a transdermal drug delivery system for this drug. So the objective of this present work is to formulate and evaluate the matrix type transdermal drug delivery systems of captopril, with different polymer combinations and penetration enhancers. MethodsEight formulations (F1–F8) were prepared by the solvent casting technique using varying proportions of polymers such as hydroxypropyl methylcellulose (HPMC), polyethylene glycol (PEG) 400, along with the permeation enhancers such as menthol and aloe vera at different concentrations. ResultsThe FTIR results showed no abnormal peaks and thus concluded that no incompatibility between the drug and polymers. The skin irritation studies were performed on rabbits, the results showed no noticeable skin reactions, pointed out the compatibility of drug as well as polymer matrix with the skin. The uniformity of drug content was evidenced by low standard deviation (S.D) values. High folding endurance (>280) revealed that the prepared films have good flexibility. The weight of patches were uniform and thickness varied from 0.05 to 0.13 mm. Ex vivo permeation studies through excised rat skin were carried out using modified Franz diffusion cell, and the results showed that film (F6) containing HPMC and PEG 400 (1:1) with menthol as a permeation enhancer demonstrated the highest drug permeation (90.04%) at 24 h (p < 0.05) with the transdermal flux of 54.5 μg/cm2/h. ConclusionsThe formulation coded as F6 was found to be the ideal patch, shown the maximum drug permeation of 90.04% at the end of 24 h followed Higuchi diffusion kinetics.

Randomised, cross-over, comparative bioavailability trial of matrix type transdermal drug delivery system (TDDS) of carvedilol and hydrochlorothiazide combination in healthy human volunteers: A pilot study

The present study deals with transdermal drug delivery system (TDDS) of Carvedilol (CRV) and Hydrochlorothiazide (HCTZ). It compares the bioavailability of these two study drugs from a TDDS with conventional immediate release oral tablets in healthy volunteers. The TDDS was also evaluated for any adverse drug reaction. This was an open-label, randomised, single centre, two-treatment, two period, single dose, crossover pilot study of two formulations of cardiovascular agents. Subjects ( n = 10) were randomised to have a TDDS applied to their abdominal skin for 72 h or receive one oral tablet each of CRV and HCTZ respectively in period I, followed by 1-week washout period. They received the alternative treatment in period II. A significant improvement in bioavailability was observed with the transdermal patches over oral tablets as observed by the mean AUC (0 − t) values 4004.37 ± 180.98 and 1824.30 ± 17.43 ng h/mL respectively for CRV and HCTZ as compared to 753.46 ± 53.34 and 392.89 ± 34.23 ng h/mL respectively, with the oral tablets. The TDDS possesses significant potential for skin irritation. The TDDS developed in our laboratory produced therapeutically effective plasma concentrations of the cardiovascular agents up to a range of 60 to 72 h (in different volunteers with a mean = 66 h). It could be concluded from these observations that the TDDS meets the intended goal of at least 2 day management of stage II hypertension with application of a single transdermal patch, hence improving patient compliance over the inconvenience seen with frequent oral administration.

Design, development, physicochemical, in vitro and in vivo evaluation of monolithic matrix type transdermal patches containing nitrendipine

The matrix type transdermal drug delivery systems (patches) of Nitrendipine were prepared by film casting technique. The patches were characterized for physical, in vitro release studies and ex-vivo permeation studies (human cadaver skin). On the basis of in vitro drug release and skin permeation performance, formulation B3 was found to be better than the other formulations and it was selected as the optimized formulation. The final optimized formulation (B3) was subjected to skin irritation, pharmacokinetic, pharmacodynamic and stability studies. The maximum percentage drug release in 48 hours was 94.67 ± 3.25 for B3 and 91.43 ± 2.106 for A2 formulation. Again formulation B3 (0.0627 mg/cm2/h) and A2 (0.0566 mg/cm2/h) showed maximum skin flux in the respective series. Patches prepared with Plasdone S-630 were more flexible as compared to PVP K 30 containing patches. Patches prepared with PVP K 30 showed drug release and skin permeation at higher percentage as compared to those containing Plasdone S-630. The interaction studies carried out by comparing the results of ultraviolet, infrared, TLC and DSC analyses for the pure drug, medicated and placebo formulations indicated no chemical interaction between the drug and excipients. The TDDS was found to be free of any skin irritation as suggested by skin irritation score of 1.16 (< 2.00) under Draize score test.

Development of Nitrendipine Transdermal Patches: In vitro and Ex vivo Characterization

The aim of the investigation was to develop and evaluate matrix type transdermal drug delivery systems (TDDS) of nitrendipine (NTDP). The matrix type TDDS of NTDP were prepared by solvent evaporation technique. Ten formulations (composed of Eudragit RL 100 and Hydroxypropyl methyl cellulose in the ratios of 5:0, 4:1, 3:2, 2:3, 1:4 in formulations A1, A2, A3, A4, A5 and Eudragit RS 100 and Hydroxypropyl methyl cellulose in the same ratios in formulation B1, B2, B3, B4, B5 respectively) were prepared. All formulations carried 6 % v/w of carvone as penetration enhancer and 15% v/w of propylene glycol as plasticizer in dichloromethane and methanol as solvent system. The prepared TDDS were evaluated for in vitro release, ex vivo permeation, moisture absorption, moisture content and mechanical properties. The physicochemical interactions between nitrendipine and polymers were investigated by Fourier Transform Infrared (FTIR) Spectroscopy. The maximum drug release in 24 hrs for A series formulations was 89.29% (A4) and 86.17% for B series (B5), which are significantly (p < 0.01) different to the lowest values (57.58 for A1 and 50.64 for B1). Again formulations A4 (flux 23.51 microg/hr/cm(2)) and B5 (flux 22.98 microg/hr/cm(2)) showed maximum skin permeation in the respective series. The flux obtained with formulation A4 and B5 meets the required flux (19.10 microg/hr/cm(2)). The mechanical properties, tensile strength, elastic modulus (3.42 kg/mm(2) for A4 and 4.25 kg/mm(2) for B5) reveal that the formulations were found to be strong but not brittle. FTIR studies did not show any evidence of interaction between the drug and the polymers. Nitrendipine matrix type transdermal therapeutic systems could be prepared with the required flux having suitable mechanical properties.

In vivo characterization of monolithic matrix type transdermal drug delivery systems of pinacidil monohydrate: A technical note.

The present work aimed to characterize transdermal drug delivery systems of pinacidil monohydrate in vivo by monitoring the effect of the TDDS on blood pressure of methyl prednisolone acetate induced hypertensive rats. The blood pressure of rats was measured using a noninvasive rat BP instrument based on cuff tail technique. A significant fall in rat BP (P<.01) was observed in treatment of hypertensive rats with all the formulations, which was maintained for 48 hours. Interformulation comparison revealed that formulation B-4 was the most effective with 37.96% reduction in BP (160.33±4.96 vs 99.44±4.46 mmHg). It was concluded that a single patch application of pinacidil TDDS (B-4) can effectively control hypertension in rats for 2 days. The system holds promise for clinical studies.

Evaluation of polymerized rosin for the formulation and development of transdermal drug delivery system: A technical note

Results from the present study conclude that PR in combination with PVP and with incorporation of dibutyl phthalate (30% wt/wt) produces smooth flexible films with improved tensile strength and percentage elongation. The release rate of drug from films and permeation across skin increases with increase in drug and PVP loading but is independent of film thickness. Patches containing PR:PVP (7:3) show promise for pharmacokinetic and pharmacodynamic performance evaluation in a suitable animal model. In view of the overall results reported in the present study, it may be proposed that PR can be used in the design of a matrix type transdermal drug delivery system to prolong the drug release.

Transdermal Drug Delivery of Labetolol Hydrochloride: System Development, In Vitro; Ex Vivo and In Vivo Characterization

The aim of the present work was to develop and evaluate matrix type transdermal drug delivery systems (TDDS) of labetolol hydrochloride (L-HCL) effective for 48 hours. The TDDS were prepared by solvent evaporation technique. Six formulations (carrying Eudragit RL100:Eudragit RS 100 in 7.5:4.5, 5.0:5.0, 3.5:8.5 in formulations X-1, X-2, X-3 and Eudragit RL100:PVP K-30 in 9.0:2.0, 5.0:5.0, 4.0:7.0 in formulations Y-1, Y-2, Y-3, respectively) were prepared. All formulations carried 36% w/w of L-HCL, 10-12% w/w of enhancer dimethyl sulfoxide and 2.5-7.5% w/w of plasticizer PEG 400 in methanol-acetone solvent system. The TDDS were evaluated by in vitro drug release, ex vivo skin permeation, stability and in vivo pharmacodynamic studies. The maximum drug release for X-series was 90.26% in 48 hours (X-1) and for Y-series, it was 83.24% (Y-1). Again formulations X-1 (Kp = 0.221x10(-2) cm hr(-1)) and Y-1 (Kp = 0.210x10(-2) cm hr(-1)) exhibited the best skin permeation potential in the respective series. This might be due to higher permeability characteristics of Eudragit RL100. A shelf life of 2.38 years was predicted for the TDDS. Mean systolic BP of the experimental hypertensive rats was significantly reduced (p<0.01) on TDDS treatment. The TDDS holds promise for clinical trials.

In Vitro Release Studies on Matrix Type Transdermal Drug Delivery Systems of Naltrexone and Its Acetyl Prodrug

Matrix type acrylic adhesive transdermal patches of naltrexone (NTX) and its 3-O-acetyl ester prodrug were prepared and evaluated for drug content, thickness, and in vitro release characteristics. Among the four DURO-TAK® adhesive polymers (87-2516, 87-2054, 87-2501, and 87-2582) tested, 87-2516 proved to be the most suitable and compatible polymer for the transdermal delivery of NTX from NTX and prodrug patches. A linear relationship was observed for release flux (F) and cumulative amount (Mt) values versus 1%, 2%, and 3% drug loading at equimolar levels. The release of NTX from the patches showed a good correlation (R2 > 0.99) for Mt vs. profiles, indicating that a Higuchian matrix diffusion mechanism of drug release from the transdermal adhesive patches was obtained. Overall, the amounts of NTX released from the prodrug patches were significantly higher than from the NTX patches, at all three drug loading levels.

A comparison between povidone-ethylcellulose and povidone-eudragit transdermal dexamethasone matrix patches based on in vitro skin permeation

The present study was designed to develop a suitable matrix type transdermal drug delivery system (TDDS) of dexamethasone using blends of two different polymeric combinations, povidone (PVP) and ethylcellulose (EC) and Eudragit with PVP. Physical studies including moisture content, moisture uptake, flatness to study the stability of the formulations and in vitro dissolution of the experimental formulations were performed to determine the amount of dexamethasone present in the patches were performed and scanning electron microscopy (SEM) photographs of the prepared TDDS were taken to see the drug distribution pattern. Drug–excipient interaction studies were carried out using Fourier transform infrared (FTIR) spectroscopic technique. In vitro skin permeation study was conducted in a modified Franz's diffusion cell. All the formulations were found to be suitable for formulating in terms of physicochemical characteristics and there was no significant interaction noticed between the drug and polymers used. In vitro dissolution studies showed that the drug distribution in the matrix was homogeneous and the SEM photographs further demonstrated this. The formulations of PVP:EC provided slower and more sustained release of drug than the PVP:Eudragit formulations during skin permeation studies and the formulation PVP:EC (1:5) was found to provide the slowest release of drug. Based on the above observations, it can be reasonably concluded that PVP–EC polymers are better suited than PVP–Eudragit polymers for the development of TDDS of dexamethasone.

Transdermal Drug Delivery Systems of a Beta Blocker: Design, In Vitro, and In Vivo Characterization

The matrix type transdermal drug delivery systems (TDDS) of metoprolol were prepared by film casting technique using a fabricated stainless steel film casting apparatus and characterized in vitro by drug release, skin permeation, skin irritation, and in vivo pharmacodynamic and stability studies. Four formulations were prepared that differed in the ratio of matrix forming polymers. Formulations M-1, M-2, M-3, and M-4 were composed of Eudragit RL-100 and polyvinyl acetate with the following ratios: 2:8, 4:6, 6:4, and 8:2, respectively. All the four formulations carried 10% (w/w) of metoprolol tartrate, 5% (w/w) of dibutylphthalate, and 5% (w/w) of (±) menthol in dichloromethane:isopropyl alcohol (80:20 v/v). Cumulative amount of drug released in 48 hr from the four formulations was 79.16%, 81.17%, 85.98%, and 95.04%. The corresponding values for cumulative amount of drug permeated for the said formulations were 59.72%, 66.52%, 77.36%, and 90.38%. On the basis of in vitro drug release and skin permeation performance, formulation M-4 was found to be better than the other three formulations and it was selected as the optimized formulation. The formulation appeared to be stable when stored at 40°C and 75% RH with negligible degradation of the drug. The TDDS was found to be free of any skin irritation as suggested by skin irritation score of 1.16 (<2.00) under Draize score test. Statistically significant reduction in mean blood pressure (p <. 01) was achieved in methyl prednisolone–induced hypertensive rats on treatment with the TDDS.

Monolithic matrix type transdermal drug delivery systems of pinacidil monohydrate: in vitro characterisation

The monolithic matrix type transdermal drug delivery systems of pinacidil monohydrate (PM) were prepared by film casting technique on mercury substrate and characterised in vitro by drug release studies using paddle over disc assembly, skin permeation studies using Keshary and Chein diffusion cell on albino rat skin and drug-excipient interaction analysis. Four formulations were developed which differed in the ratio of matrix forming polymers, Eudragit RL-100 and PVP K-30, i.e. 8:2, 4:6, 2:8 and 6:4 and were coded as B-1, B-2, B-3 and B-4, respectively. All the four formulations carried 20% w/w of PM, 5% w/w of plasticiser, PEG-400 and 5% w/w of DMSO (based on total polymer weight) in isopropyl alcohol: dichloromethane (40:60) solvent system. Cumulative % of drug released in 48 h from the four formulations was 63.96, 55.95, 52.26 and 92.18%. The corresponding values for cumulative amount of drug permeated for the said formulations were 57.28, 50.35, 46.38 and 86.54%, respectively. On the basis of in vitro drug release and skin permeation performance, formulation B-4 was found to be better than the other three formulations and it was selected as the optimised formulation. The interaction studies carried out by comparing the results of assay, ultraviolet, infrared and TLC analyses for the pure drug, medicated and placebo formulations indicated no chemical interaction between the drug and excipients.

Use of X-ray crystallography for the characterization of single crystals grown in steroid containing transdermal drug delivery systems

Target of the study was to characterize crystals which had grown in steroid-containing matrix patches during short-term storage and to thereby establish a rationale for the inhibition of crystal formation in those patches in general. Matrix type transdermal drug delivery systems (TDDS) containing either 2.2% gestodene or 3.3% estradiol were free of crystals directly after their production. However, crystals of up to 800 μm in length grew during 3 months of storage at ambient temperature. The application of several analytical methods did not help to identify the crystals. This was mainly due to the fact that the adhesive matrix surrounding the crystals could not be fully removed in the course of sample preparation with routine laboratory methods and thus impaired DSC, FTIR microscopy and hot stage polarized microscopy. However, within X-ray diffractometry, the residual amorphous patch matrix did not hamper the measurement of the crystals. Thus, they were identified as estradiol hemihydrate and gestodene form I, respectively. These results suggest that steroid-containing matrix TDDS should be stabilized against drug recrystallization e.g. by the addition of suitable crystallization inhibitors. Furthermore, systems containing estradiol may be stabilized by efficient removal water.