Formulation Development of Azadirachta indica Extract as Nanosuppository to Improve its Intrarectal Delivery for the Treatment of Malaria.

BACKGROUND: Previous folkloric and experimental reports have demonstrated the antimalarial efficacy of Azadirachta indica (AZA) extracts. However, one of the major challenges facing its application for the clinical treatment of malaria is the design of an acceptable dosage form. OBJECTIVE: Consequently, we developed AZA extract-loaded nanostructured lipid carriers (NLC) for the formulation of suppositories, denoted as nanosuppositories, for intrarectal treatment of malaria. METHODS: Various batches of NLC-bearing AZA extract were formulated based on lipid matrices prepared using graded concentrations of Softisan®154 and Tetracarpidium conophorum or walnut oil. NLC was investigated by size and differential scanning calorimetry (DSC). Suppository bearing AZA extract-loaded NLC was developed using cocoa butter or theobroma oil, and their physicochemical properties were profiled. In vitro drug release and in vivo antimalarial activity (using Plasmodium berghei-infected mice) were investigated. RESULTS: NLCs exhibited sizes in nanometers ranging from 329.5 - 806.0 nm, and were amorphized as shown by DSC thermograms. Nanosuppositories were torpedo- or bullet- shaped, weighing 138 - 368 mg, softened/liquefied between 4.10 - 6.92 min, and had controlled release behaviour. In vivo antimalarial study revealed excellent antimalarial efficacy of the nanosuppositories comparable with a commercial brand (Plasmotrim®) and better than the placebo (unloaded nanosuppository), and without toxic alterations of hepatic and renal biochemical factors. CONCLUSION: Thus, AZA extract could be rationally loaded in nanostructured lipid carriers (NLC) for further development as nanosuppository and deployed as an effective alternative with optimum convenience for intrarectal treatment of malaria.

Profiling the physicochemical and solid state properties of edible Tetracarpidium conophorum oil and its admixtures for drug delivery

Abstract The study is aimed at investigating the functional physicochemical and solid state characteristics of food-grade Tetracarpidium conophorum (T. conophorum) oil for possible application in the pharmaceutical industry for drug delivery. The oil was obtained by cold hexane extraction and its physicochemical properties including viscosity, pH, peroxide, acid, and thiobarbituric acid values, nutrient content, and fatty acid profile were determined. Admixtures of the oil with Softisan®154, a hydrogenated solid lipid from palm oil, were prepared to obtain matrices which were evaluated by differential scanning calorimetry, fourier-transform infrared spectroscopy, and x-ray diffractometry. Data from the study showed that T. conophorum oil had Newtonian flow behaviour, acidic pH, insignificant presence of hyperperoxides and malondialdehyde, contains minerals including calcium, magnesium, zinc, copper, manganese, iron, selenium, and potassium, vitamins including niacin (B3), thiamine (B1), cyanocobalamine (B12), ascorbic acid (C), and tocopherol (E), and long-chain saturated and unsaturated fatty acids including n-hexadecanoic acid, 9(Z)-octadecenoic acid, and cis-13-octadecenoic acid. The lipid matrices had low crystallinity and enthalpy values with increased amorphicity, and showed no destructive intermolecular interaction or incompatibility between T. conophorum oil and Softisan® 154. In conclusion, the results have shown that, in addition to T. conophorum oil being useful as food, it will also be an important excipient for the development of novel, safe, and effective lipid-based drug delivery systems.

Development of lipid-based microsuspensions for improved ophthalmic delivery of gentamicin sulphate.

Aim: Anterior eye segment disorders are treated with eye drops and ointments, which have low ocular bioavailability necessitating the need for improved alternatives. Lipid microsuspension of gentamicin sulphate was developed for the treatment of susceptible eye diseases. Materials & methods: Lipid microsuspensions encapsulating gentamicin sulphate were produced by hot homogenization and evaluated. Ex vivo permeation and ocular irritancy tests were also conducted. Results & conclusion: Stable microsuspensions with high entrapment efficiency and satisfactory osmolarities were obtained. Release studies achieved 49-88% in vitro release at 12 h with sustained permeability of gentamicin compared with conventional gentamicin eye drop (Evril®). No irritation was observed following Draize's test. The microsuspensions have great potential as ocular delivery system of gentamicin sulphate.

Emergency medicine: magnesium sulphate injections and their pharmaceutical quality concerns.

OBJECTIVES: World Health Organization has recognized magnesium sulphate as the drug of choice for prevention and treatment of fits associated with preeclampsia and eclampsia which are amongst the leading causes of maternal morbidity and mortality. In this study, the pharmaceutical quality of magnesium sulphate injections marketed in Anambra state was assessed. METHODS: Ninety samples of magnesium sulphate obtained from the 3 senatorial zones in Anambra state were subjected to identification tests, microbiological analysis consisting of Growth promotion test, sterility and endotoxin test. Content analysis using titrimetric method and pH analysis were also carried out on the samples. RESULTS: Twenty percent (20%) of samples obtained from Onitsha failed identification test as they had no Registration number in Nigeria. All samples subjected to the microbiology tests (sterility and endotoxin test) passed. Twenty percent (20%) and thirty-three percent (33.3%) of samples sourced from Onitsha and Nnewi respectively failed the pH analysis test. All the samples passed microbiological tests and had their Active Pharmaceutical Ingredients (API) within the acceptable limit. CONCLUSIONS: This study reveals that there are still some substandard magnesium sulphate injections in circulation in the locality. The supply chain of these drugs should be monitored to ensure a reduction in the incidences of substandard magnesium sulphate and positive therapeutic outcome which translates to reduced maternal mortality associated with pre-eclampsia and eclampsia in Nigeria.

Novel Intravaginal Drug Delivery System Based on Molecularly PEGylated Lipid Matrices for Improved Antifungal Activity of Miconazole Nitrate.

The aim of this study was to investigate the potential of microparticles based on biocompatible phytolipids [Softisan® 154 (SF) (hydrogenated palm oil) and super-refined sunseed oil (SO)] and polyethylene glycol- (PEG-) 4000 to improve intravaginal delivery of miconazole nitrate (MN) for effective treatment of vulvovaginal candidiasis (VVC). Lipid matrices (LMs) consisting of rational blends of SF and SO with or without PEG-4000 were prepared by fusion and characterized and employed to formulate MN-loaded solid lipid microparticles (SLMs) by melt-homogenization. The SLMs were characterized for physicochemical properties, anticandidal activity, and stability. Spherical discrete microparticles with good physicochemical properties and mean diameters suitable for vaginal drug delivery were obtained. Formulations based on SO:SF (1:9) and containing highest concentrations of PEG-4000 (4 %w/w) and MN (3.0 %w/w) were stable and gave highest encapsulation efficiency (83.05-87.75%) and inhibition zone diameter (25.87±0.94-26.33±0.94 mm) and significantly (p<0.05) faster and more powerful fungicidal activity regarding killing rate constant values (7.10 x 10-3-1.09 x 10-2 min-1) than commercial topical solution of MN (Fungusol®) (8.00 x 10-3 min-1) and pure MN sample (5.160 x 10-3 min-1). This study has shown that MN-loaded SLMs based on molecularly PEGylated lipid matrices could provide a better option to deal with VVC.