The utility of self-emulsifying oil formulation to improve the poor solubility of the anti HIV drug CSIC

Background: CSIC (5-chloro-3-phenylsulfonylindole-2-carboxamide), a non-nucleoside reverse transcriptase inhibitor (NNRTI) has not been advanced as a therapeutic anti-HIV candidate drug due to its low aqueous solubility and poor bioavailability.Objective: The objective of this work was to formulate CSIC into self-emulsifying oil formulations for the purpose of improving its aqueous solubility and evaluating in vitro antiretroviral activity.Methods: CSIC self-emulsifying oil formulations (SEFs) were formulated and evaluated for droplet size, zeta potential, polydispersity index (PDI), viscosity, emulsification time, stability and bioactivity.Results: Results showed significantly improved solubility of CSIC in the SEFs.The concentration of co-surfactant affected the droplet size, zeta potential and polydispersity index. In vitro bioactivity studies showed that the CSIC SEFs retained full anti-HIV activity.Conclusion: The in vitro data from this first attempt to formulate CSIC SEFs suggest that improvement on the aqueous solubility of CSIC through this delivery system may accentuate its antiretroviral effectiveness in vivo via bioavailability enhancement. The formulation is therefore intended as an oral anti-HIV agent for prophylactic and therapeutic uses. © 2013 Obitte et al.; licensee BioMed Central Ltd

A Novel Self-Nanoemulsifying Drug Delivery System Based on a Homolipid from Capra Hircus for the Delivery of Indomethacin

The dissolution of hydrophobic drugs, of which indomethacin is an example, in body fluids is a limiting step in its bioavailability. The objective of this study, therefore, was to improve the aqueous solubility of indomethacin through the development of self-nanoemulsifying drug delivery systems (SNEDDS) based on blends of a homolipid from Capra hircus with either oil bean seed oil or shea butter, which occur abundantly in most parts of sub-Saharan Africa. The oleaginous materials were extracted and purified by standard methods. After stability-indicating preformulation isotropicity tests, suitable quantities of lipid blends, surfactant blend (1:1 Tween 60 and Tween 80) and cosurfactant (Span 85) were mixed together in a beaker maintained at 50 °C to form a homogenous dispersion. The SNEDDS were assessed using the following parameters: isotropicity test, aqueous dilution stability and precipitation propensity, absolute drug content, emulsification time, in vitro release performance and anti-inflammatory activity. All the formulations of the SNEDDS exhibited low precipitation propensity and excellent stability on extensive aqueous dilution, as well as high anti-inflammatory activity in rats relative to the positive control. The absolute drug contents and emulsification times all fell within narrow limits. These results may indicate that blends of homolipid from Capra hircus with either oil bean seed oil or, particularly, shea butter could confer favourable properties with respect to drug release and anti-inflammatory activity on SNEDDS for the delivery of indomethacin.Keywords: Self-nanoemulfsifying drug delivery systems, indomethacin, Capra hircus, homolipid, shea butter, oil bean seed oilNigerian Journal of Pharmaceutical Research, Vol. 8 No 1 pp. 162 - 173 (September 2010

Ultraviolet Spectrophotometric Determination of Simvastain in Pharmaceutical Dosage Forms

This study is aimed at describing an accurate, robust and reproducible ultraviolet spectrophotometric technique for the determination of simvastain in bulk and pharmaceutical dosage formulations. Samples from three different brands of simvastatin 10mg were selected for the study. Different aliquots were taken from the stock solution to obtain series of concentration. The samples were assayed for simvastatin content and absorbance readings noted. Recovery studies were carried out to validate and ascertain the accuracy of the proposed techniques. Results revealed that the label claim was in agreement with actual amount of drug found in the three different brands examined. The ultraviolet spectrophotometric technique described in this study is quite reliable, precise and validated. Thus cane be readily employed for the determination of simvastatin in bulk and pharmaceutical formulations.Keywords: Label claim, dosage formulation, simvastatin ultraviolet spectrophotometer

In Vitro Evaluation of Polysorbate -20- Based Niosomal Formulations of Salicylic Acid

Niosomes are multiparticulate non-ionic surfactant vesicular systems that consist of lipid (often cholesterol) and a non-ionic surfactant. The objective of the study was to attempt a preliminary formulation of salicylic acid into niosomes for the possible potential improvement of its dermal permeation into warty and corny skin surfaces for expected easy and fast desquamation (for warts and corns) and enhanced penetration in fungal infections. The niosomes were formulated with polysorbate-20 and cholesterol using the Lipid Film Hydration Technique. Veegum and cetylpyridinum were incorporated in subsequent batches to investigate the effect of ionic components on the stability of the niosomes. Drug release profiles in Krebs-Ringer solution and distilled water respectively were studied to also evaluate niosome stability and release characteristics. Results showed that batch A2 with a concentration ratio of 15 mM: 15 mM of polysorbate-20 and cholesterol, gave the highest encapsulation efficiency (EE), while batch A4 with a ratio of 5 mM: 5 mM recorded the least EE. The presence of the charged components had a varied effect on the stabilities, release profiles and EEs of the niosomes depending on the molar concentration and the osmotic concentration of the drug release medium. We therefore conclude that the niosomes-stabilized salicylic acid is a potential alternative formulation approach for anticipated improvement on the permeation of salicylic acid into corns, warts and some other inflammatory conditions of the skin.Keywords: nonionic surfactant, stability, encapsulation efficiency, Veegum, cetylpyridinum, vesicle, salicylic acid, wartsNigerian Journal of Pharmaceutical Research, Vol. 8 No 1 pp. 218 - 228 (September 2010

Sustained-release liquisolid compact tablets containing artemether-lumefantrine as alternate-day regimen for malaria treatment to improve patient compliance

Petra Obioma Nnamani,1,2 Agatha Adaora Ugwu,1 Emmanuel Chinedu Ibezim,1 Franklin Chimaobi Kenechukwu,1 Paul Achile Akpa,1 John-Dike Nwabueze Ogbonna,1 Nicholas Chinedu Obitte,3 Amelia Ngozi Odo,4 Maike Windbergs,2 Claus-Michael Lehr,2,5,6 Anthony Amaechi Attama1 1Drug Delivery and Nanomedicines Research Group, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka, Nigeria; 2Department of Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research, Saarland University, Saarbrücken, Germany; 3Department of Pharmaceutical Technology and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, 4Department of Human Kinetics and Health Education, University of Nigeria, Nsukka, Nigeria; 5PharmBioTec GmbH, 6Department of Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbrücken, Germany Abstract: The present study aimed to develop low-dose liquisolid tablets of two antimalarial drugs artemether–lumefantrine (AL) from a nanostructured lipid carrier (NLC) of lumefantrine (LUM) and estimate the potential of AL as an oral delivery system in malariogenic Wistar mice. LUM-NLCs were prepared by hot homogenization using Precirol® ATO 5/Transcutol® HP and tallow fat/Transcutol® HP optimized systems containing 3:1 ratios of the lipids, respectively, as the matrices. LUM-NLC characteristics, including morphology, particle size, zeta potential, encapsulation efficiency, yield, pH-dependent stability, and interaction studies, were investigated. Optimized LUM-NLCs were mixed with artemether powder and other dry ingredients and the resultant powder evaluated for micromeritics. Subsequent AL liquisolid tablets were tested for in vitro drug release and in vivo antiplasmodial activity in mice infected with Plasmodium berghei berghei (NK 65). Results showed that optimized LUM-NLC were stable, spherical, polydispersed but nanometric. Percentage yield and encapsulation efficiency were ~92% and 93% for Precirol® ATO 5/Transcutol® HP batch, then 81% and 95% for tallow fat/Transcutol® HP batch while LUM was amorphous in NLC matrix. In vitro AL release from liquisolid compacts revealed initial burst release and subsequent sustained release. Liquisolid tablet compacts formulated with Precirol® ATO 5/Transcutol® HP-AL4 achieved higher LUM release in simulated intestinal fluid (84.32%) than tallow fat/Transcutol® HP-BL3 (77.9%). Non-Fickian (anomalous) diffusion and super case II transport were the predominant mechanisms of drug release. Equal parasitemia reduction was observed for both batches of tablet compacts (~92%), superior to the reduction obtained with commercial antimalarial formulations: Coartem® tablets (86%) and chloroquine phosphate tablets (66%). No significant difference (P<0.05) in parasite reduction between double (4/24 mg/kg) and single (2/12 mg/kg) strength doses of AL compacts was observed. Our result highlights that AL could be formulated in much lower doses (4/24 mg/kg), for once-in-two days oral administration to improve patient compliance, which is currently not obtainable with conventional AL dosage forms. Keywords: malaria, artemisinin-based combination therapy, antiplasmodial activity, liquisolid compacts, nanostructured lipid carrier