Formulation and Evaluation of Glutaraldehyde-Crosslinked Chitosan Microparticles for the Delivery of Ibuprofen

Tropical Journal of Pharmaceutical Research is indexed by Science Citation Index (Purpose: Toformulate glutaraldehyde-cross-linked chitosan-based microparticles and evaluate its suitability for the delivery of ibuprofen, a BCS class II drug.Methods: Ibuprofen-loaded chitosan microparticles were prepared by emulsification-cross-linking technique using glutaraldehyde saturated toluene (GST) as the cross-linking agent. The microparticles were characterized with respect to morphology, particle size, microparticle yield and entrapment efficiency. The swelling behaviour of the particles and ibuprofen release were assessed in both simulated gastric fluid (SGF) without pepsin (pH 1.2) and simulated intestinal fluid (SIF) withoutpancreatin (pH 7.4).Results: Discrete and free-flowing microparticles of size range 100.05 ± 8.82 to 326.70 ± 10.43 ìm were obtained. The microparticles had a high yield (69.2 to 99.2 %) and exhibited greater water sorption capacity in SIF (122.2 %) than in SGF (60 %). Furthermore, the microparticles cross-linked with 10 ml of GST entrapped the highest amount of drug (23.32 ± 0.97 %) while those cross-linked with 25 ml GST had the highest yield of the microparticles (99.19 % ), and highest water sorption in SIF (122.2 %). Up to 93.6 % of the entrapped drug was released in SIF from microparticles cross-linked with 25 ml of GST. Drug release from microparticles cross-linked with 20 and 30 ml each of GST showed a biphasic pattern.Conclusions: Entrapment of ibuprofen in glutaraldehyde-cross-linked chitosan microparticles can be exploited to target and control the release of the drug and possibly reduce its gastro-erosive side effects.Keywords: Chitosan microparticles, Ibuprofen, Oral delivery, Gastrointestinal, Glutaraldehyde

Formulation and Release Characteristics of Zidovudine-Loaded Solidified Lipid Microparticles

Purpose: To formulate and determine the release profile of zidovudine (AZT)-loaded solidified lipid microparticles (SLMs).Methods: Different concentrations (0, 1, 2, 3 and 5 %w/w) of zidovudine (AZT) were formulated into microparticles in melt dispersion of Phospholipon® 90H and goat fat in the ratio 1:1, 2:1, 2:3 and 1:3 followed by lyophilization. They were characterized for particle size, yield, entrapment efficiency (EE) and loading capacity (LC). In vitro release kinetics and mechanism of release were assessed sequentially in simulated gastric fluid (SGF, pH 1.2)and simulated intestinal fluid (SIF, pH 7.2).Results: The ratio 1: 1 formulation was the most stable in terms of physical observation.. Particle size analysis indicated that the particles were irregular in shape with size ranging from 5.10 ± 0.10 to 13.40 ± 2.20 μm. Yield decreased with increase in drug concentrations in the SLMs formulations. EE data showed that the microparticles containing 1 % w/w of AZT had the highest entrapment efficiency of 74.0 ± 0.03 %. LC also decreased with increase in concentration of AZT. AZT tablet released most of its content within 5 min with a sharp decrease in the concentration but the SLMs maintained its release for 8 to 12 h in different batchesConclusion: The results show that drug content has influence on drug release from the SLMs, but not on the mechanism of release. Furthermore, dose dumping was avoided and drug release mechanism was mostly non-Fickian while for the reference (commercial) tablet, it was Fickian.Keywords: Phospholipon® 90H, Solidified lipid microparticles, Solidified reverse micellar microparticle, Zidovudine

Moringa oleifera leaf extract potentiates anti-pseudomonal activity of ciprofloxacin

The aim of this study was to evaluate the in vitro antimicrobial interaction between the ethanol leaf extract of Moringa oleifera (MO), which is used in Nigeria as a dietary supplement, and ciprofloxacin (Cp), a flouroquinolone antibiotic. Preliminary antimicrobial screening of the ethanol extract of M. oleifera and ciprofloxacin was determined in vitro using the agar dilution method. The antimicrobial interaction between these agents was evaluated by the Checkerboard technique using Staphylococcus aureus and Pseudomonas aeruginosa as test organisms. The minimum inhibitory concentration (MIC) values of  the extract against S. aureus and P. aeruginosa were 25.0 and 50.0 mg/mL, respectively, while that of ciprofloxacin were 0.00062 and 0.0005 mg/mL against S. aureus and P. aeruginosa, respectively. The antibacterial interaction studies indicated that  the combinations predominantly showed additive effects at Cp : MO ratios of 8:2, 7:3, 6:4 and 5:5 against S. aureus while Cp : MO ratios of 9:1, 8:2, 7:3 and 6:4 yielded predominantly synergistic effect against P. aeruginosa. Other combination ratios had no MIC, hence no observed effect. This study has demonstrated that the ethanol leaf extract of M. oleifera possesses potent antibacterial effect against S. aureus and P. aeruginosa. Overall, the combined antimicrobial effect of the interaction between the extract and ciprofloxacin was predominantly synergistic against P. aeruginosa. Regarding its relevance, this study has provided a preliminary evidence of some kind of antibacterial interaction between ethanol extract of M. oleifera leaf and ciprofloxacin against P. aeruginosa and has established that the use of M. oleifera concurrently with ciprofloxacin would yield greater effectiveness in the treatment of infections in which P. aeruginosa is implicated than when either ciprofloxacin or the extract is used alone.Keywords: Moringa oleifera leaf, antibacterial interaction, checkerboard technique, Staphylococcus aureus, Pseudomonas aeruginosa, ciprofloxacinAfrican Journal of Biotechnology, Vol 13(31) 3516-352

Volatile oil May Account for the Antibiotic Effect of the Leaves of Ocimum gratissimum

Volatile oil was extracted from shredded Ocimum gratissimum leaves using a clavenger-type apparatus. Standard cream formulated from this volatile oil has been found to exhibit growth inhibitory activity using a modification of the checkerboard technique on selected test organisms - Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa. An interaction study with gentamicin cream predominantly showed synergism. The volatile oil may contribute to the use of the leaf extracts in folk medicines for the treatment of infective disorders.Keywords: Ocimum gratissimum, Volatile oil, Gentamicin, Staphylococcus aureus, Bacillus subtili

Evaluation of the microbiological quality and stability of folic acid tablets formulated with sorghum starch

The objective of this study was to investigate the microbiological quality and stability of folic acid tablets formulated with sorghum starch as a binder and to compare them with folic acid tablets formulated with corn starch BP, a standard binder. The microbiological quality of the starches, the formulated granules and folic acid tablets prepared by wet granulation, at specific periods of time under varying temperature and humidity conditions was investigated. Results indicated that maize starch had a level of microbial contaminants, comparable with the locally extracted sorghum starch. The level of microbial contamination, which was higher when non-sterile distilled water was used as the diluting medium than when sterile distilled water was employed, was shown to be dependent onboth the temperature and relative humidity, with high humidity supporting microbial growth in the products. Folic acid tablets formulated with the two different starches exhibited lower level of microbial contaminants than the raw corn and sorgum starches, indicating possible denaturation of themainly vegetative organisms during tableting. Further bioevaluation is advocated to assess the effect of compression during tableting on the level of microbial contamination.Keywords: Folic acid, stability, sorgum starch, microbioligical quality, tablets

Novel lipid-based dermal microgels of Neobacin®

This study investigates the potential of novel microgles based on solid lipid microparticles (SLMs) as a sustained delivery system for neobacin®, a topical antibiotic drug powder. Matrices generated from sunseed oil and goat fat (1:9, 2:8 and 3:7) was surface-modified with Phospholipon® 90G and employed to formulate SLM-based microgels. The microgels were characterized in terms of in vivo wound healing in rats, in vitro permeation, membrane drug retention studies and antimicrobial activity against various microorganisms using standard cup-plate agar diffusion method. The 3:7 microgels exhibited sustained release property, achieving 34% drug permeation over 12 h, 64% membrane drug retention and largest growth inhibition zone diameters (IZD) on all organisms, whereas commercial neobacin® gel achieved 35% drug permeation at 4 h and 72% membrane drug retention. In vivo wound healing followed this order 3:7>1:9>2:8 better than neobacin® powder. Neobacin® microgel formulation despite rapid degradation possessed greater wound healing and antimicrobial property than the conventional powder form of neobacin®.  Key words: Microgels, surface-modified solid lipid microparticles, sustained release, neobacin®

Evaluation of Hydrogels Based on Poloxamer 407 and Polyacrylic Acids for Enhanced Topical Activity of Gentamicin against Susceptible Infections

Purpose: To formulate hydrogels based on poloxamer 407 and polyacrylic acids (Carbopols® 971P and 974P), and evaluate its suitability for enhanced topical delivery of gentamicin, a potent but highly toxic aminoglycoside antibiotic.Methods: Topical hydrogels of gentamicin were produced using poloxamer 407 and polyacrlic acids (Carbopols® 971P and 974P), and evaluated in terms of drug content, pH, physical assessment, viscosity and stability. In vitro antimicrobial drug release was conducted using four microorganisms –Escherichia coli, Salmonella typhi, Staphylococcus aureus and  Pseudomonas aeruginosa.Results: Stable gentamicin-loaded hydrogels with good encapsulation efficiency (maximum EE% of 85.76 to 90.66 %) as well as greater zones of inhibition against all organisms (maximum range: 22.34 ± 2.35 to 29.40 ± 3.07 mm) than commercially available gentamicin ointment and pure sample of gentamicin (p < 0.05), were produced. Overall, poloxamer 407 hydrogels of gentamicin gave the most desirable properties in terms of pH, viscosity and rapid concentration and time-dependent antibacterial activity on all tested micro-organisms, superior to polyacrylic acids hydrogels of gentamicin.Conclusion: This study demonstrates that poloxamer 407 hydrogels of gentamicin may offer a promising approach for topical delivery of gentamicin for the treatment of skin infections caused by gentamicin-susceptible bacteria.Keywords: Hydrogels, Gentamicin, Polyacrylic acid, Viscosity, Bioactivity, Poloxamer 40

Topical Delivery of Miconazole-Loaded Microemulsion: Formulation Design and Evaluation

Microemulsions are frequently employed as drug delivery systems to enhance the bioavailability of the incorporated drug via topical, oral and systemic routes. The objective of the present study was to develop a topical microemulsion and evaluate its potential as drug delivery vehicle for a sparingly water soluble antifungal agent, miconazole nitrate. Various combinations of surfactant-cosurfactant (Tween 80 and propylene glycol), castor oil and water were used to construct pseudoternary phase diagrams from which the most efficient emulsifying region was chosen for preparing miconazole nitrate-loaded topical microemulsion. The microemulsion was characterized with respect to globule size, morphology, viscosity, pH and conductivity. The ex vivo release of miconazole from the drug-loaded microemulsion was studied using Franz diffusion apparatus in which the donor compartment was separated from the receptor compartment by a freshly excised hairless rat skin. Results obtained showed that a homogeneous and thermodynamically stable miconazole nitrate-loaded topical microemulsion was successfully prepared with an oil, surfactant and cosurfactant mixture. The ex vivo release study revealed significant drug release from the topical microemulsion, with permeation coefficient values that ranged from 2.5 x 10-6 cm/s to 9.8 x 10-6 cm/s depending on the surfactant-cosurfactant ratio. This study has shown that the problem of poor solubility and bioavailability of miconazole nitrate could be surmounted by incorporating it into lipid-based drug delivery systems such as microemulsions, and that topical microemulsion is a promising tool for percutaneous delivery of miconazole nitrate, thus encouraging further development of this formulation. &#160

Preparation and Characterization of Poloxamer 188 solid dispersions of Indomethacin

The objective of this study was to improve the dissolution rate of a hydrophobic non-steroidal anti-inflammatory drug (NSAID), indomethacin (IMC) which shows poor bioavailability due to its poor solubility in the gastrointestinal fluids. Poloxamer 188 (PXM 188) was employed as a hydrophilic carrier at various IMC: PXM 188 ratios to prepare IMC-loaded solid dispersions (SDs) using the fusion method. Characterization based on surface morphology, particle size, absolute drug content and moisture sorption properties were carried out on the SDs. The in vitro release of IMC from the SDs was performed in simulated intestinal fluid without pancreatin (SIF, pH 7.4 ). Results indicate that discrete and irregularly-shaped SDs of mean particle size in the range 2.10 ± 0.68 to 6.95 ± 0.98 μm, which were stable over 3 months, were obtained. The moisture sorption studies indicated the amorphous/ microcrystalline state of IMC in the SDs, which also exhibited good encapsulation efficiency (EE%) and marked increase in the dissolution rate of IMC from the SDs when compared to pure IMC. Increasing PXM 188 concentration in SD formulation resulted in an increase in the dissolution rate of the drug (IMC). This study has shown that IMC/PXM 188 SDs could be a promising approach for dissolution and bioavailability enhancement of the poorly water-soluble drug, IMC. Journal of Pharmaceutical and Allied Sciences, Vol. 9 No. 3 (2012

Novel carrier system for enhancing oral delivery of metformin

This study was designed to evaluate the potential of PEGylated lipospheres as carriers for improved oral delivery of metformin hydrochloride. Lipospheres were prepared by melt-emulsification method using Phospholipon® 90H in beeswax (30%w/w) as the lipid matrix containing increasing quantities of PEG 4000 and characterized. The in vitro and in vivo release of the formulations was evaluated. Results show that the particle size and encapsulation efficiency ranged from 33.18±1.75 - 83.23±6.05 μm and 85 to 93%, respectively. Drug release showed a biphasic pattern and was found to follow the Higuchi square root model. Metformin hydrochloride -loaded lipospheres lowered basal blood glucose levels by 60% and sustained antihyperglycemia for over 20 h. This study suggests that encapsulation of metformin hydrochloride into PEGylated lipospheres could reduce its dosing frequency and the associated side effects resulting from high doses of metformin hydrochloride as seen in conventional tablet formulations.Keywords: PEGylated, lipospheres, metformin hydrochloride, anti-diabeticAfrican Journal of Biotechnology, Vol 13(50) 4568-457