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Title: Rheological & Release Characteristics of Drugs of Different Solubilities from Semisolid Matrix Filled in Hard Gelatin Capsule
Authors: Sultana, Misbah
Keywords: Pharmacy (Pharmaceutics)
Issue Date: 2016
Publisher: University of the Punjab, Lahore
Abstract: The re-introduced liquid/semisolid matrix technology, in recent past encompasses filling of hard gelatin capsules for thixotropic system at ambient and thermosoftened system at elevated temperature. Formulations in both of the above systems may contain dissolved or dispersed drugs. In the present work thixotropic gels were prepared using a series of hydrophilic poloxamers (Pluronic/Synperonic L31, L43, L62, L64, L92) of different viscosities and composition of polyoxyethhylene and polyoxypropylenein co-polymers thickened with hydrophilic silicon dioxide (Aerosil®A200) to form gel structure. Model drugs of varying solubilities, isoniazid, metronidazole, paracetamol and mefenamic acid were dispersed in gels of above poloxamers. The gel formulations were filled into hard gelatin capsules via syringe. The rheological characteristics, dispersion stability, and FTIR of the gels with and without drugs were investigated. The gels with drugs were additionally characterized for their release pattern. In preliminary studies, twenty separate gels of poloxamers L31, L64 were thickened with concentrations 1 to 10% w/w of Aerosil® A200 to incorporate isoniazid (unsifted, 10% w/w). Different concentration of Aerosil® A200 affected dispersion stability as well as release of the drug incorporated into gels. All gels were thixotropic and shear thinning. A little change in apparent viscosity on storage upto 30 days was noted. Disperse phase sedimentation was not observed with more viscous poloxamer and with higher concentration of silicon dioxide. Higher concentration of Aerosil® A200 resulted into stronger gel structure between silicon dioxide and poloxamers and thereby, hindered release of drug from a gel. Rheograms of poloxamers, L31 and L64 confirmed their Newtonian behaviour, in contrast to the thixotropic behaviour of all gels made with Aerosil® A200 concentrations (1-10% w/w) and 10% w/w isoniazid. Therefore, ii in-vitro release of highly water soluble drug, isoniazid could be controlled by poloxamer/A200 thixotropic gel system which depended upon concentration of Aerosil® A200, viscosity of poloxamer and the aqueous solubility of drug. In the further work, the effect of selected concentration of Aerosil® A200 (8% w/w) and five liquid poloxamers of different viscosities on release of drugs with characterized particle size (180-250 μm) and of different from semi solid matrix/ thixotropic gel filled into hard gelatin capsules was tested by in-vitro dissolution test. The drugs with different solublities used in this study were isoniazid, metronidazole, paracetamol and mefenamic acid. The interaction of drug in gel formulations was also determined by Fourier transform infrared (FTIR) spectroscopy. The release of drugs from different formulations was related to their aqueous solubility, viscosity of poloxamers, and poloxamer’s polyoxyethylene and polyoxypropylene proportions. In most of the formulations drug remains dispersed over a period of one month depending upon the viscosity of gels. Most of the gels showed little change in apparent viscosity on storage. The apparent viscosity for each gel was found to be dependent on the viscosity of poloxamers from which the gel was prepared. Like in preliminary work, rheograms of five pure poloxamers showed Newtonian behaviour whereas each gel exhibited thixotropic and shear thinning. In-vitro dissolution data of drugs from their respective stable gels followed first order kinetics. No chemical interaction or incompatibilities between drugs and polymers were noted by FTIR. Long term stability studies at International conference on harmonization (ICH) recommended conditions of temperature/relative humidity (30C/65% RH) over one year revealed that almost all the gels retained their rheological, dispersion stability, release profile and chemical integrity. Thus, the hydrophilic semisolid matrix (gels) made by mixing poloxamer and Aerosil® (A200) was suitable for filling into hard gelatin capsules because of their rheological characteristics. The release of drugs with different solubilities could be modified by using iii poloxamers of different viscosity. Overall present research study demonstrates the effect of silicon dioxide on the microstructure of the gel prepared with various poloxamers which is evident from the rheological studies, FTIR and release pattern of the drugs.
Gov't Doc #: 14267
Appears in Collections:PhD Thesis of All Public / Private Sector Universities / DAIs.

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