Pharmacokinetics and in vivo chemosuppressive activity studies on cryptolepine hydrochloride and cryptolepine hydrochloride-loaded gelatine nanoformulation designed for parenteral administration for the treatment of malaria.

The main objective of this investigation was to establish the pharmacokinetics profile and in vivo chemosuppressive activities of cryptolepine hydrochloride-loaded gelatine nanoparticles (CHN) designed for parenteral administration for the treatment of malaria in comparison to the drug free in solution (CHS). Single-dose pharmacokinetics was investigated in Wistar rats by administering CHN or CHS (equivalent to 10 mg/kg of drug) by IV bolus injection via the lateral tail vein. The drug concentration in plasma was monitored over a 24-h period following administration. Chemosuppressive activity was investigated in Wistar rats challenged with P berghei parasites. Animals were given a daily dose of either CHN or CHS, equivalent to 2.5-100 mg/kg by intraperitoneal injection. The level of parasitaemia was determined by light microscopy by examining Giemsa-stained thin blood smears prepared from the tail end on day four of infection. It was found that CHN attained a higher (4.5-folds) area under the curve (AUC (0-24)) compared to CHS. CHS however produced a higher volume of distribution (4-folds). Distribution and elimination rates were higher with CHS which resulted in a lower (11.7 h) elimination half-life compared to that of CHN (21.85 h). The superior pharmacokinetic profile of CHN translated into superior chemosuppressive activity at all dose levels relative to CHS. As a conclusion, loading cryptolepine hydrochloride into gelatine nanoparticles improved both pharmacokinetics and in vivo antiplasmodial activity of the compound with the highest chemosuppression (97.89 ± 3.10) produced by 100 mg/kg of CHN.

Design and in vitro evaluation of gentamicin-Eudragit microspheres intended for intra-ocular administration.

The conditions of preparation of gentamicin sulfate microspheres with high drug loading and a particle size less than 5 micro m, using a double-emulsion-solvent evaporation technique, intended for intra-ocular administration are described. The microspheres were prepared from poly methacrylate (Eudragit RS and RL) polymers cross-linked with polyvinyl alcohol. The parameters that improved the incorporation efficiency of gentamicin in the microspheres and controlled the particle size and surface morphology were investigated. Modifying the secondary aqueous phase by partially saturating it with various concentrations of either KCl or gentamicin increased the incorporation efficiency of the drug and affected the mean diameters of the microspheres. However, these characteristics were not altered when the initial drug loading was increased in the formulations. The modified gentamicin microspheres exhibited a smooth surface with an incorporation efficiency rate of 12.59% and a mean diameter of 4.06 micro m. The antimicrobial efficiency of gentamicin released from the modified particles against selected Gram-positive and -negative organisms including Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa confirmed that the entrapped gentamicin seemed to remain unaltered by the encapsulation process.

Stability studies of aspirin-magaldrate double layer tablets.

Accelerated stability testing was performed on aspirin-magaldrate double layer tablets as well as aspirin-maalox marketed double layer tablets (Ascriptin) in order to evaluate the effect of the presence of the alkaline moieties of the antacid (magaldrate and maalox) on the chemical stability of aspirin. The results were compared simultaneously with that obtained from the marketed Aspro plain tablets. The results revealed that the presence of the alkaline moieties in the tested tablets has increased the rate of aspirin decomposition and reduced its shelf-life. This effect was more pronounced for aspirin tablets containing magaldrate antacid. Determination of shelf-lives at 25 degrees C for the prepared and the marketed tablets was carried out using Arrhenius plots and the results showed that they were 35, 34.5 and 13.5 months for Aspro, Ascriptin and aspirin-magaldrate double layer tablets, respectively. The effect of storage for 50 days and at different temperatures, on the crushing strength and the disintegration time of the prepared and the marked tablets showed a slight decrease in the disintegration time and the crushing strength of the tablets as the storage temperature increased. Aspro tablets did not produce the same results. The in vitro release data of the prepared aspirin-magaldrate double layer tablets and the marketed Ascriptin tablets stored for 50 days and at different storage temperatures as well as Aspro tablets stored at 70 degrees C were best fitted to the first-order kinetics model. The release data of Aspro tablets stored at 50 and 60 degrees C for 50 days were best fitted to Higuchi's model.