الفهرس 
AcknowledgementOnly 14 pages are availabe for public view
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Abstract
Drug delivery systems intended for colon targeting are beneficial either when a local or when a systemic treatment is required. In the first case, advantages include reduced drug dose and therefore decreased incidence of systemic side effects, thus ensuring patient compliance. In the second case, advantages include among others, improved drug bioavailability due to longer retention time.
This work aimed at preparing and evaluating dosage forms for a drug acting directly on smooth muscle of the colon in condition of irritable bowel syndrome (spastic colon) and for a drug to be absorbed and act systemically in chronic asthmatic patients. The present thesis is divided into two parts.
Part I: “Colon targetinf of mebeverine HCI from pH-dependent release tablet formulations”
It was concerned with the development of colon-targeted mebeverine HC1 coated tablets using pH-controlled system. A tablet core (Tc) containing 25% mebeverine HC1 was prepared by direct compression in the presence of Avicel PH 101 and carboxymethylcellulose sodium(CMC Sod.).
The tablet core was tested for drug content, content uniformity, hardness, weight variation and thickness. pH-dependent enteric polymers were used for coating the tablet core namely; cellulose acetate phthalate (CAP) and Eudragit L 100 (EL100) in mixture with hydroxypropylmethylcellulose 4000 (HPMC 4000) in different ratios.
Two sets of coated tablet formulations were prepared. The first set was prepared by compression coating of the prepared core with a mixture of HPMC 4000 and CAP in ratios of!:! (Fl), 1:3 (F2) and 1:5 (F3) orHPMC 4000 and EL100 1:3 (F4). The second set (F5) was prepared by compression coating of the core with HPMC 6 cp, then dipping in isopropyl alcohol containing 12.5% w/v ELi 00 and 1.25% w/w PEG 400 as a plasticizer.
The coated tablets complied with quality control tests namely: drug content, uniformity of drug content, weight variation, tablet hardness, thickness and porosity. Swelling study was performed, based on the calculation of swelling index, for Fl, F2, F4 and F5 in 0.1 N HC1 (2 hours) then at pH 6.8. For all formulations, swelling index increased slightly in 0.1 N HC1 but at pH 6.8, they showed a bimodal swelling patterrr followed by complete erosion after 28 hours.
The drug release rate was determined using USP dissolution apparatus II in 0.1 N HCI (2 hours) followed by a buffer of pH 6.8 for 28 hours. Concerning all the formulations, no or negligible release occurred in the first 2 hours; less than 20% of the drug was released in the following 3 hours. from 5 to 12 hours, the formulations coated with CAP (Fl, F2 and F3) exhibited a more retarded release rate than those coated with EL100 (F4 and F5) due to hydrogen bonding between CAP and HPMC.
Correlation coefficients (r) calculated for the First order and Higuchi plots for all the
tablet formulations were both high, indicating that the mechanism of drug release is a
complex one that may be partly attributed to the polymer mixture used. Results of swelling
paralleled to those of release for all formulations.