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. used were of analytical grade. Preparation of TDDS. Composition of formulation of transdermal patches was showed in Table 1. The polymeric solution (10%. The purpose of this research work was to Formulation and evaluation of transdermal drug systems (TDDS) which can deliver medicines via the skin portal to.
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Formulation and evaluation of transdermal drug-delivery system of isosorbide dinitrate. The purpose of this study was to develop a reservoir-type transdermal delivery system for isosorbide dinitrate ISDN. The developed patch consisted of five layers from bottom to top, namely, a temporary liner, an adhesive layer, a rate-controlling membrane, a reservoir and a backing.
The effects of chemical penetration enhancers, reservoir evaluatiob and rate-controlling membranes on the release behaviour of ISDN from the transdermal patch were studied, and the in vitro release of ISDN from the developed patch was studied and compared with the commercially available ISDN patch.
Moreover, the tcds release ratio of the commercially available ISDN patch in 48 h was up to Transdermal-patch technology has advanced tremendously since the first scopolamine patch tdss introduced into the market in It can be attributed to today’s advanced patch-making technology, through which nearly a billion patches are manufactured every year Prausnitz, Langer, These transdermal patches are classified into three types: Isosorbide dinitrate ISDN is commonly used for the therapy of stable angina pectoris and is traditionally administrated via oral or sublingual routes.
However, loss of consciousness appears in patients when angina pectoris breaks out, and thus it is difficult for patients to take the medicine by themselves. Additionally, administrated orally ISDN has low bioavailability, owing to its high first-pass metabolism in the gastrointestinal tract and liver.
Moreover, the critical point of anti-anginal therapy depends, to a certain extent, on the ability of the drug to produce an immediate effect Johnson, Gladigau, Schnelle, ; Fung, ; Taylor et al. Thus, transdermal delivery may be an appropriate administration route for ISDN.
Among the ISDN transdermal patches designed and reported previously, the drug-in-adhesive patches are the simplest and the most commonly used design. The in vitro release results show that the release kinetics of ISDN is a first-order process, suggesting that the outwards moving of ISDN from the adhesive is associated with a passive diffusion process. Drug release from a drug-in-adhesive patch depends directly upon the drug concentration in the patch and follows first-order kinetics.
Formulation and Evaluation of Transdermal Patch of Repaglinide
However, reservoir-type transdermal drug delivery could be observed the zero-order kinetics. The rate controlling membrane, as a most important component in the reservoir-type transdermal patch, was responsible for controlling drug delivery. The rate-controlling membranes anx in previous publications included ethyl cellulose Lewis, Pandey, Udupa,collagen and chitosan Thacharodi, Rao,ethylene-vinyl acetate EVA Shen et al.
Previous work in our lab has proven that acrylate polymers, as a new type of formulstion membranes, could control clonidine HCl solution release with zero order Zhan et al. But, such film-like acrylate polymers have not been applied in the production of patches to date. The aim of this study was to develop a reservoir-type transdermal patch of ISDN with acrylate polymer as the rate-controlling membrane, which could keep drug release at a constant rate for at least 48 h.
The effects of chemical penetration enhancers, reservoir materials and rate-controlling membranes on the release behaviour of ISDN permeation across the transdermal patch were studied. Methanol was of HPLC grade.
Frandol r tape was purchased from Yamanuchi Pharm JP 40 mg in 40 cm 2. All other chemicals were of reagent grade and used as received.
The structure of the transdermal patch consisted of five layers, namely, a temporary liner, an adhesive layer, a rate-controlling membrane, a reservoir and a backing Figure 1.
First, the adhesive solution was coated onto the temporary liner 3M, Scotchpak TM and was allowed to dry completely. Then, a polyacrylate membrane, as a rate-controlling membrane, was pressed over the adhesive layer.
Then, the reservoir layer was pressed onto the rate-controlling membrane. Last, the polyester film laminate 3M, Scotchpak TMas a backing layer, covered the reservoir. The temporary liner and the backing layer were then heat-sealed and cut to the appropriate sizes. The patch was stored in a sealed aluminium pouch to minimise the loss of solvent.
The construction of the ISDN transdermal patch. The solution was cooled before adding 0. We used a previously reported method that had already been used in our lab to prepare three rate-controlling membranes Figure 2that is, membrane M1 made of monomers A, B and C1 Zhan et al.
The ratio of the monomers in each membrane was 4: The structure of acrylate monomers. The drug reservoir layer was separated carefully from the glass plate, and then pressed tightly on the rate-controlling membrane.
The mixed solution was casted onto a glass plate with cm 2 areas, and then the plate was put in an oven Hanzhou Huier Equipment Co.
The drug reservoir layer was carefully separated from the glass plate and tightly attached to the rate-controlling membrane. The preparation of the drug reservoir with a penetration enhancer followed the same procedure as the preparation of the PVA reservoir layer. The patch thickness was measured using a digital meter Shanghai Measuring and Cutting Tools Factory, China at five different places.
The average and standard deviation of five readings were calculated for three batches of the optimised formulation with an area of 1 cm 2. Three different patches from three batches, each with an area of 1 cm 2were weighed individually, and the average weight and standard deviation was calculated.
The solution was filtered, diluted suitably and measured by HPLC. Hairless rat skin was used to evaluate the effects of penetration enhancers on the permeation and to evaluate the permeation of ISDN release from the optimised developed patch. The skin was isolated from hairless rats male, weeks old and g in weight that were obtained from Slac Lab. Hairless rats were euthanised by carbon dioxide asphyxiation prior to the permeation experiment and its abdominal skin was carefully excised using scissors and forceps.
The underlying subcutaneous fat was removed from the excised skin and the thus-obtained abdominal skin ca. Permeation experiments were carried out to evaluate the rate-controlling membrane, the drug reservoirs, the penetration enhancers and the integral developed patch.
The tested component was cut into appropriate sizes and mounted on a modified Franz diffusion assembly Ng e t al. When the tested component was the integral developed patch, the temporary line should be removed, and the dermis side of the skin faced the receptor compartment. The effective diffusion area was 0. The receptor compartment was filled with The receptor medium was maintained at At pre-determined time intervals 0.
The samples were analysed by HPLC. Data acquisition and processing were dealt with by Waters Empower professional software. The mobile phase was a mixture of methanol and water in the volume ratio of The mobile phase was filtered through a 0. The accuracy was determined by recovery studies.
The experiments were conducted in triplicate. The intra-day variability was checked at three time points on the same day, and the inter-day variability was checked on three consecutive days. A set of sample solutions were prepared to ascertain the specificity of the method. Assuring the sink conditions in the in vitro release experiment is very important.
According to the requirements of the sink conditions, the volume of the receptor medium was generally greater than times that of the saturation point of ISDN in this medium. Thus, the saturated solubility of ISDN in the receptor medium needed to be quantified.
ISDN was added to the flask with The saturated solution was filtered and then measured by HPLC. The intercept on the x -axis was taken as the lag time T Lh. All of the release experiments were repeated three times from independent batches, and mean values of the permeation rates with standard deviations were calculated. Student’s t -test and analysis of variance ANOVA were used to statistically determine significant differences.
The p value used in this study was 0. The percentage recoveries of the three concentrations from low tdvs high were found to be The method specificity was assessed by comparing the chromatograms obtained from the sample solutions Figure 4 ; the retention time of ISDN observed from the HPLC was 6. Chromatograph from HPLC obtained from different sample solutions.
The highest drug content in our research was 5 mg the concentration in donor compartment: Thus, the receptor media volume was nine times greater than the saturation point trds the sink conditions were achieved during the permeation experiment.
In fact, other researchers also used water as the receptor media for the purpose of simulating evaluatiion human physiological environment Zhao et al. To screen a suitable rate-controlling membrane, different concentrations of ISDN in 1,2-propylene glycol solution 1. The release behaviours of ISDN across different rate-controlling membranes were studied over 24 h.
It was found that the rate-controlling membrane marked M1 showed the highest value of evaluxtion rates under the same drug-donor concentration, as shown in Figure 5. This result could be explained by the pore sizes of membrane M1, which was fabricated randomly by polymer evaluafion.
As polyacrylates are non-degradable polymers, they are controlled formulatkon molecules across the pores in the membrane instead of evaliation, erosion or dissolution of the polymer. The shorter side chain of monomer C1 would occupy the pore’s inner space less compared with C2 and C3, as a result of the drug molecules release across the membrane M1 more easily.
Membrane M1 also showed higher permeation rates compared to M2 and M3 when the tested drug was clonidine HCl Zhan et al. The permeation of ISDN through different ratecontrolling membranes. So, the PVA was chosen to perform latter experiment.
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To screen the penetration enhancers, three penetrations covering a broad range of lipophilicity values log P values of penetrations amounted to The weight ratio of the penetration enhancers were tfds in a previously published paper Halina; Krzysztof; Stanislaw, ; Chen et al. Physicochemical properties of penetration enhancers.
Comparison of the p values from the permeation rates in four formulation groups. Although the penetration enhancers had no effects when the drug transported across the rate-controlling membrane, M1, it was well known that the penetration enhancers had serious effects on the skin in general. To further illustrate how the penetration enhancers affected the permeation rates, the release behaviours of ISDN in the formulation groups F2, F3, F4 and F5 transporting across the rats’ ex-vivo skin were studied.
The fastest rate of permeation in the case of urea was explained by it having the lowest molecular weight when compared to ydds more lipophilic penetrations Table IIas well as by its permeation-enhancing potential for the hydrophilic drugs because the value of log P of ISDN was 0.
In vitro release of ISDN in fformulation formulations with amd penetration enhancers across through the rats’ ex-vivo skin. Actually, the excised animal skin could not represent the real permeation of drugs transporting through human skin. But, the animal skin is frequently used as a replacement for human skin, because the human xnd is difficult to acquire under ethical principles.