Assessment of palmitoyl and sulphate conjugated glycol chitosan for development of polymeric micelles.

INTRODUCTION: Amphiphilic copolymers are capable of forming core shell-like structures at the critical micellar concentration (CMC); hence, they can serve as drug carriers. Thus, in the present work, polymeric micelles based on novel chitosan derivative were synthesized. METHODS: Block copolymer of palmitoyl glycol chitosan sulfate (PGCS) was prepared by grafting palmitoyl and sulfate groups serving as hydrophobic and hydrophilic fractions, respectively. Then, fourier transform infrared spectra (FTIR) and spectral changes in iodine/iodide mixture were carried out. RESULTS: FTIR studies confirmed the formation of palmitoyl glycol chitosan sulfate (PGCS) and spectral changes in iodine/iodide mixture indicated CMC which lies in the range of 0.003-0.2 mg/ml. CONCLUSION: Therefore, our study indicated that polymeric micelles based on palmitoyl glycol chitosan sulphate could be used as a prospective carrier for water insoluble drugs.

Preparation and characterization of hybrid pH-sensitive hydrogels of chitosan-co-acrylic acid for controlled release of verapamil.

In the present work crosslinked hydrogels based on chitosan (CS) and acrylic acid (AA) were prepared by free radical polymerization with various feed compositions using N,N methylenebisacrylamide (MBA) as crosslinking agent. Benzoyl peroxide was used as catalyst. Fourier transform infrared spectra (FTIR) confirmed the formation of the crosslinked hydrogels. This hydrogel is formed due to electrostatic interaction between cationic groups in CS and anionic groups in AA. Prepared hydrogels were used for dynamic and equilibrium swelling studies. For swelling behavior, effect of pH, polymeric and monomeric compositions and degree of crosslinking were investigated. Swelling studies were performed in USP phosphate buffer solutions of varying pH 1.2, 5.5, 6.5 and 7.5. Results showed that swelling increased by increasing AA contents in structure of hydrogels in solutions of higher pH values. This is due to the presence of more carboxylic groups available for ionization. On the other hand by increasing the chitosan content swelling increased in a solution of acidic pH, but this swelling was not significant and it is due to ionization of amine groups present in the structure of hydrogel. Swelling decreased with increase in crosslinking ratio owing to tighter hydrogel structure. Porosity and sol-gel fraction were also measured. With increase in CS and AA contents porosity and gel fraction increased, whereas by increasing MBA content porosity decreased and gel fraction increased. Furthermore, diffusion coefficient (D) and the network parameters i.e., the average molecular weight between crosslinks (M(c)), polymer volume fraction in swollen state (V(2s)), number of repeating units between crosslinks (M(r)) and crosslinking density (q) were calculated using Flory-Rehner theory. Selected samples were loaded with a model drug verapamil. Release of verapamil depends on the ratios of CS/AA, degree of crosslinking and pH of the medium. The release mechanisms were studied by fitting experimental data to model equations and calculating the corresponding parameters. The result showed that the kinetics of drug release from the hydrogels in both pH 1.2 and 7.5 buffer solutions was mainly non-Fickian diffusion.

Encapsulation and characterization of controlled release flurbiprofen loaded microspheres using beeswax as an encapsulating agent.

The aim of the present study was to extend the use of flurbiprofen in clinical settings by avoiding its harmful gastric effects. For this purpose, we designed the controlled release solid lipid flurbiprofen microspheres (SLFM) by emulsion congealing technique. Drug was entrapped into gastro resistant biodegradable beeswax microspheres which were prepared at different drug/beeswax ratios 1:1, 1:2 and 1:3 using gelatin and tween 20 as emulsifying agents. The effect of emulsifiers and the effect drug/beeswax ratios were studied on hydration rate, encapsulating efficiency, micromeritic properties, scanning electron microscopy (SEM), fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (X-RD) analysis and in vitro drug release at pH 1.2 for 2 h and at pH 6.8 for 10 h. SEM revealed that microspheres made with tween 20 were smooth while microspheres made with gelatin showed porous morphology, however, they were all spherical in nature. The practical yield (recovery) showed a dependence on drug-beeswax ratio and it was variable from 53 to 84%. High loading encapsulating efficiency of flurbiprofen from 8 to 94% was achieved. FTIR and DSC analysis confirmed the absence of any drug polymer interaction indicating drug stability during microencapsulation. X-RD of pure flurbiprofen shows sharp peaks, which decreases on encapsulation, indicating decrease in the crystallinity of drug in microspheres. The micromeritic studies confirmed the presence of excellent and good flow properties of microspheres. Entrapment efficiency, morphology, practical yield, hydration rate, flow properties demonstrated their dependence on the HLB value of emulsifiers and emulsifiers with higher HLB were found more appropriate for effective microencapsulation of flurbiprofen. The release kinetics followed zero order mechanism of drug release at pH 6.8. Release pattern depends on the morphology of flurbiprofen microspheres and amount of beeswax used in the microspheres preparation. The microspheres prepared with high HLB values i.e., tween 20 showed effective control of drug release from microspheres. The absence of drug release at pH 1.2 proved the suitability of beeswax for its use as a gastro resistant material.

Polymeric micelles of ammonium palmitoyl glycol chitosan and solubilization of camptothecin.

Chitosan is a polysaccharide possessing biodegradable and biocompatible properties. Chitosan and its derivatives are used as excipients in drug delivery, as mucoadhesive polymers, and as a permeation enhancer for drug delivery in vitro at mucosal epithelia; and micelles of chitosan derivatives are used for solubilization of hydrophobic drug. Twenty-five samples of ammonium palmitoyl glycol chitosan were synthesized after reacting glycol chitosan with palmitic acid N-hydroxysuccinimide and methyl iodide with different concentration of hydrophobic and hydrophilic component. The objective was to identify suitable combinations of hydrophilicity and hydrophobicity which dissolve maximum water-insoluble camptothecin drug. In conclusion, the more hydrophilic and hydrophobic polymers are not suitable for solubilization of camptothecin.