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Matrix type transdermal drug delivery system TDDS of Pregabalin was prepared by the solvent evaporation technique. Propylene glycol was used as plasticizer and DMSO was incorporated as a permeation enhancer. Formulated transdermal patches were charachterised for their physicochemical parameters like thickness, weight variation, flatness, tensile strength, folding endurance, moisture content, moisture uptake and drug content uniformity. Patches were evaluated for their in-vitro drug release profile and ex-vivo skin permeation studies.
Patches were also subjected to stability studies and skin irritation studies to determine their compatibility with skin. Result of evaluation studies revealed that Pregabalin can be administered as a controlled drug delivery system to reduce frequency of drug administration. But this hypothesis requires further confirmation via in-vivo pharmacodynamic and pharmacokinetic studies in animal and human models.
It also finds its use in peripheral diabetic neuropathy, fibromyalgia and post-therapeutic neuralgia. So, the objective of present work is to develop a controlled release dosage form of Pregabalin other than oral route and injectables. Hence, a non-invasive system in the form of transdermal patch of Pregabalin was thought to be developed and evaluated with the aim of achieving controlled release of Pregabalin over a prolong time period so that frequency of drug administration will be minimised.
Transdermal drug delivery has certain advantages over other systems of drug administration which in turn leads to increase patient compliance.
Its non-invasive nature, ease of application and removal, predetermined rate of drug permeation, increased bioavailability of drug and decreased hepatic metabolism; all these factors make this system most suitable for systemic delivery of drug over long time periods of 24hrs. Therefore, market of transdermal patches has made tremendous growth in recent years 2, 3. Technology Employed: Transdermal patch of Pregabalin was prepared by solvent evaporation technology.
In this technology, mixture of polymer and drug solution was spread as a film on a suitable support glass, mercury, aluminium foil etc. After evaporation of solvent, dried residue is the required patch containing drug trapped in the matrix of polymer 4, 5. The patch thus obtained was then evaluated for various parameters like physicochemical parameters, drug content, drug release profile and for skin irritation studies. Preparation of different Placebo Polymeric Films: Different placebo patches are prepared by employing hit and trial method on various combinations of different hydrophilic and hydrophobic polymers 6, 7.
From these various placebo patches, the combination having desired properties to support a transdermal drug delivery system is selected for incorporation of drug. Different combinations of polymers are as follows:. Table 1 below shows the composition and characterization of placebo patches prepared by using different polymers in different ratios. These polymers were then dissolved in solvent system containing water: methanol Drug solution containing plasticizer and penetration enhancer in appropriate concentration was added to the polymer solution.
The polymer solution thus obtained was spread in petri dish previously coated with a lubricant castor oil. This petri dish was placed in tray dryer maintained at temperature not more than 30 o C for about 6hrs. After 6hrs petri dish was taken out of tray dryer and patch was removed and observed for its physical appearance and for various other parameters.
Such patches were found to be uniform, smooth and flexible. Physical Appearance: Formulated patches were evaluated for their physical appearance, uniformity, entrapment of any air bubble or precipitation of drug, which on a large part determines patient acceptability of the patch and also therapeutic efficacy 8.
Thickness of rectangular patch 2x2cms was determined at three different points and average thickness was calculated. Same was performed for other patches also. Thickness of each individual patch should not deviate significantly from each other 8.
Weight Variation: Weight variation was studied by individually weighing 10 randomly selected patches and average weight was calculated. The individual weight should not deviate significantly from the average weight 8, 9. Folding Endurance: Evaluation of folding endurance involves determining the folding capacity of the patches.
Folding endurance is determined by repeatedly folding the patch at the same place until it break The number of times the patch could be folded at the same place without breaking is folding endurance value. Tensile Strength: Mechanical properties of the polymeric patches were conveniently determined by measuring their tensile strength 11, The tensile strength of the patches was determined by using an assembly designed to measure the tensile strength of the patch.
Assembly consist of a pan hanged by using a strong thread and the other end of the thread was attached with the centre of the patch. The whole assembly was held like a beam balance and weights were kept on the pan.
Weights required to break the patch was noted. Tensile strength was then calculated using the following formula:. Moisture Uptake: Patch was kept in a desiccator at room temperature for 24hrs. Moisture Content: The prepared patches were weighed individually and kept in a desiccator containing calcium chloride at room temperature for 24hrs.
The patches were weighed again after a specified interval until they show a constant weight. The percent moisture content was calculated using following formula. Complete dissolution was achieved by placing the solution containing patch on shaker for about 24 hrs. Solution was then filtered and drug content was estimated spectrophotometrically at nm after suitable dilution. In-Vitro Permeation Studies: Permeation studies are carried out in order to determine transition of drug from patch to skin microcirculation.
In this study, synthetic membrane like cellulose nitrate was placed between the donor and receptor compartment of Franz diffusion cell 12, Receptor compartment was filled with phosphate buffer of pH 7. Transdermal patch was placed upon the cellulose nitrate membrane facing towards the donor compartment. The other side of cellulose nitrate membrane was towards the receptor compartment having phosphate buffer. The receiver compartment was maintained at room temperature and was continuously stirred with the help of magnetic stirrer.
Samples were withdrawn at specific time interval and equal amount of phosphate buffer was replaced each time to maintain volume of receptor compartment at a constant level. Samples withdrawn were then analysed for their absorbance and concentration was then calculated. Table 4 below shows the in-vitro permeation profile of drug from each batch. Rat was sacrificed and skin was removed from abdominal portion Appropriate size of sin was shaved using depilatory cream and this skin was then used as a barrier between donor and receptor compartment of Franz diffusion cell.
Transdermal patch P 1 was placed upon it facing towards stratum corneum of the skin. Receptor compartment was filled with Phosphate buffer pH 7. Samples were withdrawn at different time interval and equal amount of phosphate buffer was then added to the receptor compartment in order to maintain volume of the receptor compartment constant.
Samples thus withdrawn were analysed by means of U. V Spectrophotometer in order to estimate amount of drug present in the sample. Stability Studies: Stability of a TDDS is a very important factor to be considered while formulating such system because it affects therapeutic efficacy of the system as well as patient compliance.
Here, formulated patches were wrapped in aluminium foil and kept at room temperature for a period of 30 days. Formulation P 1 was selected for this study as this formulation seemed quite promising throughout all evaluation studies performed previously on this formulation. Formulation was also characterised for other parameters like physical appearance and physical parameters and drug content uniformity. Procedure adopted for evaluation of formulation after 30 days was same as used earlier that is by using Franz diffusion cell containing phosphate buffer of pH 7.
Samples withdrawn at different time intervals were analysed by U. V spectrophotometer to determine their concentration. Table 7 shows the drug release profile data after 30 days. Skin Irritation Studies: Skin irritation studies were carried out in order to detect irritation and sensitization under conditions of maximal stress which may occur over a prolong contact with the skin surface.
For this study rat was used as an animal model. Patch P 1 2x2 cm 2 was applied to the shaved skin of the rat on one side of the back and secured using adhesive tape. On other back side of the rat, control patch without drug was placed in a similar manner. Animal was then kept under observation for a period of 48hrs to detect any sign of erythma, redness, sensitization or any other allergic reaction.
Stability studies indicate that drug release rate of transdermal patch does not reveal significant variation. It was found to be Skin irritation studies show no sign of erythma or any other skin irritation reaction, so it can be concluded that neither the drug nor any polymer or excipient was found to cause adverse effects on skin, hence, patch was found to be compatible with skin.
Result of all evaluation parameters was found to be satisfactory within permissible limits. Hence this non-invasive, compatible patch with ease of application and removal may find increase patient compliance but present work required to be supported by further studies involving in-vivo pharmacodynamic and pharmacokinetic studies in animal and human models.
Meenakshi Bajpai and Ms. Monika Sachdeva, who provided their kind help, efforts and support for the completion of this work. Download: Cited By: 8. Publications, Chien Y. Banker G. Naik A. Kumar A. Chandrashekhar N. Damecha D. Benson A. Matteucci M. Baert B. Guang M. Bull Volume 28 2 ,
Formulation and evaluation of transdermal drug delivery of topiramate
Matrix type transdermal drug delivery system TDDS of Pregabalin was prepared by the solvent evaporation technique. Propylene glycol was used as plasticizer and DMSO was incorporated as a permeation enhancer. Formulated transdermal patches were charachterised for their physicochemical parameters like thickness, weight variation, flatness, tensile strength, folding endurance, moisture content, moisture uptake and drug content uniformity. Patches were evaluated for their in-vitro drug release profile and ex-vivo skin permeation studies. Patches were also subjected to stability studies and skin irritation studies to determine their compatibility with skin. Result of evaluation studies revealed that Pregabalin can be administered as a controlled drug delivery system to reduce frequency of drug administration. But this hypothesis requires further confirmation via in-vivo pharmacodynamic and pharmacokinetic studies in animal and human models.
Formulation and Evaluation of Transdermal Patch of Repaglinide
Transdermal drug delivery system TDDS was designed to sustain the release and improve the bioavailability of drug and patient compliance. Among the various types of transdermal patches, matrix dispersion type systems disperse the drug in the solvent along with the polymers and solvent is allowed to evaporate forming a homogeneous drug-polymer matrix. The objective of the present study was to design and formulate TDDS of topiramate TPM and to evaluate their extended release in vitro and ex vivo. In the present study, an attempt has been made to develop a matrix-type transdermal therapeutic system comprising TPM with different ratios of hydrophilic and hydrophobic polymeric combinations using solvent casting technique. The physicochemical compatibility of the drug and the polymers was studied by Fourier transform infrared spectroscopy.