Hemangi PATEL

ABSTRACT 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. Tizanidine Hydrochloride, an imidazoline derivative, is α2-adrenergic agonist and centrally acting myotonolytic skeletal muscle relaxant with a structure unrelated to other muscle relaxants. Tizanidine hydrochloride having lower bioavailability (40%) due to first pass metabolism by the liver. So, bioavailability can be increased by transdermal route. The object of the study was to develop Matrix Type Transdermal Patch of Tizanidine HCl. Transdermal patches were prepared by solvent evaporation method using Eudragit RS 100 and PVP polymers by incorporating Polyethylene Glycol and Propylene Glycol as plasticizer. Standard procedures were used to analyze the prepared films for various physicochemical parameters(weight variation, thickness uniformity, % moisture content, %moisture uptake, Folding Endurance and drug content). drug release (Franz diffusion cell) and skin irritation test. The drug and polymer compatibility was studied by DSC. Among all the formulations, the F1 prepared by using Eudragit RS 100 and PEG 400 as plasticizer is the better formulation for control release of drug up to 6 hrs of time. Results of the present study encouraged that the Tizanidine HCl with Eudragit RS 100 transdermal patch can be used as controlled drug delivery system and frequency of administration can be minimized. The kinetic models used were Zero order, First order Higuchi’s and Korsmeyer–Peppas model. Transdermal patches were successfully prepared for Tizanidine Hydrochloride and their evaluation suggested excellent quality and uniformity in patch characteristics. This can have potential applications in therapeutic area offering advantages in terms of reduced dosing frequency, improved patient compliance and bioavailability. Keywords: Tizanidine Hydrochloride, Eudragit RS 100, Matrix type, polyvinylpyrrolidone, Transdermal patche

The main aim of the formulation was to prepare Nasal in situ gel for cyproheptadine HCl using an admixture of pH sensitive polymer i.e. carbopol 940 and viscosifying agent i.e. HPMC K100 M in order to achieve a sustained release of drug. The Nasal in situ gel containing cyproheptadine HCl was prepared by taking carbopol 940 and HPMC K100 M in different ratios. The concentrations of carbopol 940 and HPMC K100 M were investigated using 32 full factorial design. The parameters determined were pH, physical appearance, drug content, gelling capacity, Mucoadhesive strength, viscosity, in vitro drug release. The drug excipient compatibility study was carried out by using Fourier transform infrared spectroscopy(FTIR). The pH values in situ gels were between 5.0 to 6.0. Drug content values were between 98% to 100%. The release profile of in situ gels exhibited a sustained release of cyproheptadine HCl. Drug release was dependent on the concentration of carbopol 940 and concentration of HPMC K100 M. Cyproheptadine HCl was successfully formulated as an nasal in situ gel to deliver drug for 8 h. The drug release of the nasal in situ gel decreased with decrease in concentration carbopol 940 and viscosity increased with increasing levels of HPMC K100 M. The drug release and viscosity could be adjusted and modified by varying the ratio of polymer and viscosifying agent. The optimized formulation F8 (0.6 % w/v carbopol 940 and 0.4 % w/v of HPMC K100 M) provide drug release of 8 h and release drug immediately after it is instilled into the nose. Formulation F8 was seen to be stable after one month of stability study.

In July 2005, the FDA issued an alert for healthcare professionals regarding dissolution media effects on drug release from a SR dosage form not involving a hydrophilic matrix, i.e., alcohol-Palladone interaction1. Hence, the aim of present works was to check the effect of Hydro alcoholic dissolution media in sustained release polymer and investigate the influence of hydro-alcoholic media on drug release for metoprolol Succinate sustained release tablets. Metoprolol succinate is a drug used for Hypertension and it is suitable drug candidate for extended release due to its short Half-life. Combination of HPMC K4M and HPMC K100M, Carbopol 934 P, Chitosan, HPMC K100 M: Ethyl Cellulose (4:1), Sodium-Carboxyl Methyl Cellulose were used as a polymer matrix to control the release of Metoprolol succinate up to 12 hrs. The Sustained release tablets of Metoprolol succinate were prepared by Wet granulation method. All the tablets were evaluated for the Pre-compression and post Compression Parameter. In-vitro dissolution study was done in Normal Dissolution Media, Phosphate Buffer pH 6.8 and also in 10 %, 20 %, 30 % and 40% v/v ethanol solutions for up to 12 hrs. All HPMC, Chitosan, Sodium-CMC preparation did not fail in hydro-alcoholic media, while Carbopol 934 P preparation show highest differences compare to all other. The highest dissolution was found to be more than 80 % in 12 hours for 40 % v/v ethanol solution in Carbopol 934 P ,which was not comply with standard range of drug release by USFDA and show dose dumping of Formulation. Kinetic model application confirmed that the release of Metoprolol succinate follows zero order as well as Korsmeyer-Peppas model. From these studies it was concluded that Carbopol 934 P formulation indicated highest signs of a potential dose dumping compare with other formulation.