Enhanced anti-inflammatory and ulcerogenicity of Ibuprofen microsphere formulations using Irvingia wombolu fat (IRW) and moringa oil (MO) as co-lipids.

Ibuprofen is a member of the propionic acid class of nonsteroidal anti-inflammatory drugs (NSAIDs) with anti-inflammatory, analgesic, and antipyretic activities used to relieve a variety of pains. The objective of this study was to formulate, characterize and evaluate the in vitro and in vivo properties of ibuprofen formulated as solid lipid microspheres (SLMs) for enhanced delivery. The mixtures of Irvingia wombolu fat (IRW) and moringa oil (MO) each with Phospholipon® 90G (PL90G) at the ratio of 2:1 w/w were prepared by fusion, characterized and used to prepare SLMs. The SLMS were thereafter evaluated using the following parameters: particle size and morphology, stability, and encapsulation efficiency EE (%). In vitro release was carried out in phosphate buffer (pH 7.4). The ibuprofen based SLMs were also evaluated for anti-inflammatory and anti-ulcer effects using animal models. The pH showed significant increase after two months of formulation with a maximum value of 6.4 while the EE obtained were 95.6, 89.4 and 61.6% for SLMs formulated with lipid matrix of Phospholipon® 90G (1% and 2%), and MO (1%) respectively. The in vitro release showed maximum release of 87.8 and 98.97% of the two different lipid-based formulations while anti-inflammatory effect was up to 89.90% after 5 h of inducing inflammation. The SLMs did not show any lesion thus conferring gastroprotection on the formulations. The SLMs exhibited good anti-inflammatory property with gastroprotective action.

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.

Anti-Inflammatory and Gastroprotective Properties of Aspirin - Entrapped Solid Lipid Microparticles.

BACKGROUND: Aspirin is a nonsteroidal anti-inflammatory drug that is very effective in the treatment of inflammation and other health conditions, however, it causes gastric irritation. Recently, researchers have developed patents (US9757529, 2019) of inhalable aspirin for rapid absorption and circumvention of gastric irritation. OBJECTIVE: The aim of this work was to formulate aspirin-loaded lipid based formulation in order to enhance oral bioavailability and inhibit gastric irritation. METHODS: This solid lipid microparticles loaded with aspirin (SLM) was formulated by a modified cold homogenization-solvent evaporation method. In vitro studies such as in vitro drug release, particle size, Encapsulation Efficiency (EE), micromeritic properties and loading capacity were carried out. Pharmacodynamics studies such as anti-inflammatory and ulcerative properties of the SLM were also carried out in Wistar rats. RESULTS: The results showed that aspirin entrapped SLM exhibited the highest EE of 72% and particle size range of 7.60 + 0.141µm to 20.25 + 0.070µm. Formulations had about 55% drug release at 6h in simulated intestinal fluid pH 6.8. The formulations had good flowability that could facilitate filling into hard gelatin capsule shells. The SLM exhibited 100% gastroprotection against aspirin-induced ulcers (p < 0.05). The percentage of anti-inflammatory activities also showed that aspirin-entrapped SLM had 78% oedema inhibition at 7h, while the reference had 68% inhibition at 7h. CONCLUSION: Aspirin-entrapped SLM showed good sustained-release properties, enhanced antiinflammatory properties and total gastric protection from aspirin-induced ulcers and could be used as once-daily oral aspirin.

Formulation of novel sustained release rifampicin-loaded solid lipid microparticles based on structured lipid matrices from Moringa oleifera.

OBJECTIVES: To formulate sustained release rifampicin-loaded solid lipid microparticles (SLMs) using structured lipid matrices based on Moringa oil (MO) and Phospholipon 90G (P90G). METHODS: Rifampicin-loaded and unloaded SLMs were formulated by melt homogenization and characterized in terms of particle morphology and size, percentage drug content (PDC), pH stability, stability in simulated gastric fluid (SGF, pH 1.2), minimum inhibitory concentration (MIC) and in vitro release. In vivo release was studied in Wistar rats. RESULTS: Rifampicin-loaded SLMs had particle size range of 32.50 ± 2.10 to 34.0 ± 8.40 µm, highest PDC of 87.6% and showed stable pH. SLMs had good sustained release properties with about 77.1% release at 12 h in phosphate buffer (pH 6.8) and 80.3% drug release at 12 h in simulated intestinal fluid (SIF, pH 7.4). SLMs exhibited 48.51% degradation of rifampicin in SGF at 3 h, while rifampicin pure sample had 95.5% degradation. Formulations exhibited MIC range of 0.781 to 1.562, 31.25 to 62.5 and 6.25 to 12.5 µg/ml against Salmonella typhi, Escherichia coli, and Bacillus subtilis respectively and had higher in vivo absorption than the reference rifampicin (p < 0.05). CONCLUSION: Rifampicin-loaded SLMs could be used once daily for the treatment tuberculosis.

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.

Evaluation of dika wax-soybean oil-based artesunate-loaded lipospheres: in vitro-in vivo correlation studies.

OBJECTIVES: To formulate and evaluate artesunate-loaded lipospheres and study the in vitro-in vivo correlations (IV-IVC). MATERIALS AND METHODS: Lipospheres were formulated by melt homogenisation using structured lipid matrices consisting of (1:3 and 1:6) soybean oil and dika wax and were characterised in vitro and in vivo. RESULTS: The small angle X-ray diffraction (SAXD) results of the lipid matrices showed prominent reflection at 2θ = 2.49°, d = 3.55 Å while, wide angle X-ray diffraction (WAXD) showed prominent reflection at 2θ = 20.83°, d = 0.42 Å. Lipospheres had maximum encapsulation efficiency of 80%, showed no significant decrease in pH with time (p < 0.05), and had sustained release properties. The ratio of the area under the curve (AUC) of the lipospheres and the tablets gave bioavailability enhancement factor of 2.108. CONCLUSION: Artesunate-loaded lipospheres could be used orally or parenterally once daily, for the treatment of malaria.

Analgesic and Micromeritic evaluations of SRMS-based oral Lipospheres of Diclofenac Potassium.

The objective of our work was to study the micromeritic properties of lyophilized diclofenac potassium-loaded lipospheres and to evaluate in vivo, the analgesic properties of diclofenac potassium in the lipospheres in addition to other in vitro properties. Solidified reverse micellar solutions were prepared by fusion using 1:1, 2:1, and 1:2% w/w of Phospholipon(®) 90H and Softisan(®) 154. Diclofenac potassium (1, 3, and 5% w/w) was incorporated into the solidified reverse micellar solutions. Solidified reverse micellar solutions-based lipospheres were formulated by melt homogenization techniques using Ultra-Turrax homogenizer, and thereafter lyophilized to obtain water-free lipospheres. The lipospheres were characterized in terms of particle size and morphology, stability, thermal analysis, drug content, encapsulation efficiency, and loading capacity. The flow properties of the lipospheres were studied using both direct and indirect methods of assessing flow. The analgesic properties of the lipospheres were studied using the hot plate method. Results obtained showed that the yield of diclofenac potassium-loaded lipospheres was high and the particle size ranged from 0.61±0.07 to 2.55±0.04 µm. The lipospheres had high encapsulation efficiency of 95%, which was affected by the amount of drug loaded, while the loading capacity increased with the increase in drug loading. Diclofenac potassium-loaded lipospheres exhibited poor flow. The formulations exhibited good analgesic effect compared with the reference and had 84 to 86% drug release at 13 h. The lipospheres based on solidified reverse micellar solutions could be used for oral delivery of diclofenac potassium.

Formulation and Evaluation of Alstonia boonei Stem Bark Powder Tablets.

The aim of this work was to formulate Alstonia boonei dried stem bark powder into tablets by wet granulation method using acacia, gelatine and sodium carboxymethyl cellulose as binders at concentrations of 1, 2, 4 and 8% w/w. The phytochemistry of the stem bark of Alstonia boonei was evaluated. The micromeritic properties of the granules prepared were studied. The tablets were evaluated using the necessary official and unofficial tests. The results of the phytochemical analysis showed that alkaloids, tannins, steroids, saponins, glycosides, flavonoids and terpenoids were present while anthroquinones and acidcompounds were absent. Micromeritic studies showed that Alstonia boonei granules had good flowability. The formulated tablets complied with British Pharmacopoeial specification for weight uniformity, hardness (≥5 kgf) and tablet friability (<1%). For disintegration test, tablets formulated with gelatine and acacia at concentrations of 1, 2 and 4% w/w complied with Pharmacopoeial specification. However, tablets formulated with SCMC (1-8% w/w) and 8% w/w of acacia and gelatine failed the disintegration tests (Disintegration time more than 15 min).