Evaluation of the Properties of Encapsulated Stavudine Microparticulate Lipid-based Drug Delivery System in Immunocompromised Wistar Rats.

BACKGROUND: Lipid-based formulations have been confirmed to lower some side effects of drugs and can be tailor-made to offer sustained drug release of drugs with short half-life like stavudine. AIM: This study aimed to evaluate the immunomodulatory properties of stavudine-loaded solid lipid microparticles (SLMs) using immunocompromised Wistar rats. METHODS: The SLMs were formulated by the homogenization method. The optimized batches were used for further in vivo studies. The effect of formulation on the CD4 count and the haematological properties of immunocompromised Wistar rats were studied. RESULTS: The particle size range was 4 -8 µm, EE range was 85-93 % and maximum drug release was observed at 10 h. The CD4 cells increased from 115 ± 3.17 cell/mm3 at day zero to 495 ± 5.64 cell/mm3 at day 14 of treatment and 538 ± 6.31 cell/mm3 at day 21. The red blood cells increased from 2.64 ± 1.58 (x 106/mm3) at day zero to 6.96 ± 3.47 (x 106/mm3) at day 14 and 7.85 ± 3.64 (x 106/mm3) at day 21. PCV increased significantly (p < 0.05) to about 42-50 % at day 21 in the groups that received the SLMs formulations. White blood cells (WBC) also were 12 x 103/mm3, for SLM formulations, while the rats that received plain stavudine exhibited WBC of 9.6 x 103/mm3 at day 21. The histopathological studies revealed that oral stavudine-loaded SLMs had no significant damage to the kidney, liver, spleen and the brain of Wistar rats. CONCLUSION: The formulations exhibited significantly higher immunomodulatory properties than plain stavudine (p<0.05) and showed good properties for once daily oral administration and could be a better alternative to plain stavudine tablets for the management of patients living with HIV.

Formulation, characterization and anti-malarial activity of homolipid-based artemether microparticles.

The anti-malarial activity of artemether is dependent on its bioavailability. The purpose of the research is to improve the solubility, bioavailability and therapeutic efficacy of lipophilic artemether using homolipid-based microparticles. Irvingia fat was extracted from Irvingia gabonensis var. excelsa (Irvingia wombolu), and its lipid matrices (LM) with Phospholipon(®) 90G (P90G) were characterized by differential scanning calorimetry (DSC) and wide angle X-ray diffraction (WAXD). Solid lipid microparticles were formulated, characterized, filled and compressed into capsules and tablets, respectively, and drug release studied. In vivo anti-plasmodial activity of artemether SLMs was evaluated in mice. The crystallinity of the phyto-lipid reduced in the presence of P90G, which was integrated into the irvingia fat crystal lattice. SLM dispersions with 3:1 irvingia fat/P90G composition showed higher diffusion and permeability through dialysis membrane while lower proportion of P90G (9:1 LM) favored increased dissolution rate of artemether from capsules (p<0.05). Significant increase (p<0.05) in % plasmodial growth inhibition and reduced parasitemia were observed in mice administered with the SLM dispersions compared with the controls. Therefore, SLMs prepared with composite mixtures of a homolipid and P90G could be used to improve the solubility, dissolution, permeability, bioavailability and anti-malarial efficacy of artemether.

Formulation and characterization of hydrochlorothiazide solid lipid microparticles based on lipid matrices of Irvingia fat.

INTRODUCTION: The purpose of this study was to improve the solubilization, bioavailability, and permeability of hydrochlorothiazide (HCTZ) by the formulation and characterization of HCTZ solid lipid microparticles (SLMs) based on fat derived from Irvingia gabonensis var. excelsa (Irvingia wombolu) and Phospholipon(®)90G (P90G). MATERIALS AND METHODS: Irvingia fat was extracted from the nut of I. gabonensis var. excelsa using petroleum ether (40-60°C). HCTZ loaded SLM were formulated using hot homogenization method with 5% w/w Irvingia fat/P90G at each of 1:0, 9:1, 4:1, and 3:1 ratios, 1% w/w HCTZ, 1.5% w/w Labrasol(®) surfactant and distilled water. Subsequently, particle size analysis, pH, syringeability, drug encapsulation efficiency (EE%), yield, freeze-thaw cycle test, drug release, diffusion, and kinetics were evaluated. RESULTS: The SLM dispersions showed a particle size range of 10.15 ± 2.36 to 13.50 ± 6.88 µm and pH of 5.6-6.4 while dispersions containing 3:1 Irvingia fat/P90G passed through most of the needles (18G, 21G, and 22G) after syringeability studies. A single freeze-thaw cycle caused loss of physical integrity. The EE% of the SLMs were ≥80%, with high yield. The highest drug release and diffusion was observed with SLMs prepared with 3:1 Irvingia fat-P90G mixture (HDP3) and Higuchi model best described the kinetics of the HCTZ release by Fickian diffusion. CONCLUSION: The release and permeability of HCTZ was improved by its incorporation into Irvingia fat and P90G (3:1) as SLMs.

Sustained-release diclofenac potassium-loaded solid lipid microparticle based on solidified reverse micellar solution: in vitro and in vivo evaluation.

OBJECTIVE: To formulate sustained-release diclofenac potassium-loaded solid lipid microparticles (SLMs) based on solidified reverse micellar solution (SRMS) and to evaluate the in vitro and in vivo properties. METHODS: SRMS consisting of mixtures of Phospholipon® 90H and Softisan® 154 were used to formulate diclofenac potassium-loaded SLMs. Characterization based on the particle size and morphology, stability and encapsulation efficiency (EE%) were carried out on the SLMs. In vitro release was carried out in simulated intestinal fluid (pH 7.5). Anti-inflammatory and ulcerogenic properties were studied using rats. RESULTS: Maximum EE% of 95%, 94% and 93% were obtained for SLMs formulated with SRMS 1:1, 2:1 and 1:2, respectively. In vitro release showed about 85-90% drug release at 13 h. Diclofenac potassium-loaded SLMs showed good anti-inflammatory and gastro-protective properties. CONCLUSION: Diclofenac potassium-loaded SLMs based on SRMS could be used orally or parenterally under controlled conditions, for once daily administration.