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Title: Development of Topical Hydrogel Membrances: Characterization and In-Vivo Evaluation
Authors: Ahmad, Sarfaraz
Keywords: Pharmaceutics
Issue Date: 2019
Publisher: Islamia University, Bahawalpur.
Abstract: Background and Objective In the pharmaceutical sciences, skin disorders and its topical treatment are gaining attention in advanced ways as compared to oral and traditional drug therapy. Topical targeted dug delivery with polymer gels as vehicle is to localized drug with enhanced therapeutic effect. As compared to controlled polymeric drug delivery, conventional oral and topical drug delivery has limitations of high dosage, more frequency of application and more irritation with non-compliance. Mupirocin (MP) is the better choice in skin wounds and in resistive bacterial infection when applied topically. The purpose of current study was to develop and optimize controlled release topical polymeric hydrogel membranes to deliver mupirocin locally with reduced dosage frequency. Different polymers, monomers with cross linkers in different proportions were used to formulate different types of membranes. To characterize and compare antimicrobial activity of mupirocin, In-vitro, ex-vivo and in-vivo evaluations were conducted for prolong wound and burn therapy with enhanced patient compliance. Methodology Modified free radical polymerization method was adopted for synthesis of different topical hydrogel membranes of mupirocin. Hydrogel membranes were characterized by in-vitro analysis and general characteristics, swelling studies to check the sensitivity with buffer solutions (pH 4.0, 5.5, 7.4), drug loading and in-vitro drug release studies. Structural, thermal and morphological analysis were conducted by fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), differential scanning microscopy (DSC) and scanning electron microscopy (SEM). In-vitro permeation study, ex-vivo skin deposition study and skin irritation study were also conducted to measure and quantify the amount of drug permeated and deposited. Furthermore, quantification of mupirocin in skin samples of formulations were also performed after the revalidation of developed HPLC method. In-vivo study of selected formulation was conducted to measure bacterial count after application and compares the efficacy with marketed formulation. Results Results of FTIR, TGA, DSC, SEM, in-vitro release and permeation data confirmed the development of polymeric hydrogel membranes and formulation synthesized by low molecular weight chitosan polymer (LCS) was selected as optimized for in-vivo evaluation. Percent drug release of mupirocin for chitosan based membranes was 85.78% at pH 5.5 and 93.93% at pH 7.4. Permeation flux was 121.62μg/cm2.h-1 and deposited amount was up to 1224μg/1.5cm2 respectively. Developed and revalidated HPLC method was used for quantification of all formulations that deposited in rabbit skin. Irritation study data was confirmed that developed cross-linked polymeric hydrogel membranes were non-irritant to skin. In-vivo study of surgical wound model for hydrogel membrane with marketed formulation reveal that hydrogel and MF reduced the bacterial count after treatment to 4.27±6.3 and 4.31±7.9 log 10 CFU/wound and there was non-significant difference between hydrogel membrane applied once in a day and conventional MP ointment applied three times in a day (P>0.05). Conclusion It could be concluded that hydrogel membranes of low molecular weight chitosan could be classified as better topical membranes among the developed formulations that were highly effective to deliver model drug mupirocin for long term therapy of wound healing and other infectious skin disorders as they showed better in-vitro, ex-vivo and in-vivo results. Skin irritation study data also confirmed that developed formulations were safe and non-irritant to the skin.
Gov't Doc #: 20083
Appears in Collections:PhD Thesis of All Public / Private Sector Universities / DAIs.

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