The biochemical effects of chronic administration of efavirenz, which is commonly used as part of highly active antiretroviral therapy for treatment of human immunodeficiency virus (HIV) type 1, on the intracranial auditory relay centers [i.e., the inferior colliculus (IC) and medial geniculate body (MGB)] of adult Wistar rats were carefully studied. Rats of both sexes (n Z 30), with an average weight of 200 g, were randomly assigned into treatment (n Z 15) and control (n Z 15) groups. Rats in the treatment group each received the recommended daily dose of 600 mg/70 kg (1.71 mg/200 g) of body weight of efavirenz daily for 30 days, while the control group rats received an equal volume of distilled water alone daily for 30 days. The rats were sacrificed after 30 days, and the IC and MGB were carefully removed for further biochemical assays. These analyses indicated that levels of malonyldialdehyde (MDA), a non-enzyme biomarker of oxidative stress, were significantly higher (p < 0.05) whereas levels of superoxide dismutase (SOD) were significantly lower (p < 0.05) in treated tissues than in control tissues. Chronic administration of efavirenz may therefore have an adverse effect on the auditory sensibilities by affecting the IC and MGB of adult Wistar rats.

INTRODUCTION: Bilayer floating drug delivery system is an approach which helps to overcome the shortcomings of single layered tablets. There is little or no fluctuation of drug in blood stream and tissue, while permitting control over time and site of drug release. In the current study, bilayer theophylline matrix tablets were formulated by double compression and evaluated using granules produced by polymeric granulation and simple coacervation techniques. METHODS: Bilayer floating theophylline tablets containing an immediate release layer (IRL) and sustained release layer (SRL) were prepared. Granules for the IRL section were produced by wet granulation while that for the SRL section were produced by polymeric granulation and simple coacervation techniques using Eudragit RL100 and Carboxymethylcellulose (CMC) as binder. Resulting granules were characterized for flowability and packing properties. Granules with adequate flow were compressed into flat faced tablets of 12 mm diameter using a single punch tableting machine at arbitrary load of 28 KgF on load scale. Tablets were evaluated for hardness, weight variability, disintegration, friability, swelling index, floating time, and in vitro drug release. RESULTS: The angle of repose and Hausner ratio were 29.07 ± 0.330 to 40.08 ± 0.660 and 1.07 ± 0.01 to 1.28 ± 0.01 respectively. Tablets hardness values ranged between 4.74 ± 0.36 to 9.84 ± 0.49 KgF, while percentage friability ranged between 0.5 to 1.51%. Floating lag time was between 1 ± 0.41 and 9 ± 0.71 min while the total floating time was between 1 min and 9 h. Over 50 % of drug was released within 7 h. DISCUSSION AND CONCLUSION: Drug release from the tablets showed prompt release phase and extended release phase. Thus, appropriate combination of Eudragit and CMC and the right reagent can produce well retarded bilayer floating tablets.