Abstract:
This work studied the various delivery systems (oral and parental formulations) of crude Cannabis. The stability, pharmacological and toxicological profiles of Cannabis resin in the formulations was also studied. Dried powdered leaves of Cannabis sativa L. were extracted with chloroform, the extract was concentrated to obtain an oil-based tar (resin) and its phytochemical
composition determined. The Cannabis crude resin was formulated as syrup, capsule and suppository dosage forms. The stability of the resin in the formulations was studied by accelerated stability technique. The in vivo release profile of the capsules was also studied. The antimicrobial activity of Cannabis crude resin was investigated using clinically isolated Pseudomonas aeruginosa and Staphylococcus aureus. The minimum inhibitory concentration (MIC) and killing rate constant against the organisms were determined by agar diffusion and viable count methods respectively. The anti-inflammatory effect of Cannabis crude resin and syrup formulations was studied using egg-albumin-induced paw oedema in rats. The acute toxicity (LDSo) of the crude extract was determined by the brine-shrimp method while effects on biochemical parameters (glutamate-pyruvate-transaminase, glutamate-oxaloacetate-transaminase and urea) haematological parameters (eosinophile, monocyte, neutrophiles and lymphocyte counts, packed-cell volume and red blood cells) were determined in Wistar rats after 1, 2 and 3 weeks of treatment. The internal organs (liver, heart, kidney, spleen, lungs and the brain) from the treated rats were examined histopathologically to ascertain degeneration on chronic administration of Cannabis crude resin. Results were analysed statistically using the Analysis of Variance (SPSS) and Student's t-test. Means that differed significantly were identified by the least significant difference (LSD) Post-hoc test at 95 % confidence interval i.e. (Pc0.05). The result showed that the extraction process yielded 10 % (wlw) of the Cannabis crude resin. The presence of alkaloids, glycosides, saponins, tannin, terpenes and steroids was detected in the crude resin and dried plant. Cannabis crude resin syrup was stable even without the addition of EDTA with a shelf-life of 50 days. The degradation of Cannabis crude resin syrup formulation followed a first-order kinetic with the degradation rate constant of 0.0039 min-I. At a minimum inhibitory concentration (MIC) of 12.5 mglml, the chloroform, methylene chloride, ethanol, nhexane: chloroform (1:l) and n-hexane extracts of Cannabis sativa showed significantly (Pc0.05) higher antimicrobial activity against S. aureus and Ps. aeruginosa than Penicillin G (MIC 18.0 mgfml). The crude resin syrup formulation exhibited a significant (Pc0.05) dose-related inhibition of paw edema in rats. The crude resin caused changes in biochemical and haematological parameters in a dosedependent manner with no significant increase in the first two weeks of treatment, which markedly changed at week 3. The histopathological results of the various organs showed lesions of varied intensity suggesting possible toxicity in chronic use of Cannabis crude resin. These findings suggest that crude Cannabis resin can be used for its antimicrobial and antiinflamatory effect and that its formulation into syrup favours its pharmacological activity and have good stability.
