Optimized Nanoparticles for Enhanced Oral Bioavailability of a Poorly Soluble Drug: Solid Lipid Nanoparticles Versus Nanostructured Lipid Carriers.

INTRODUCTION: Rosuvastatin calcium (ROSCa) is an anti-hyperlipidemic drug with only 20% oral bioavailability due to its low solubility and high first-pass metabolism. Therefore, the main purpose of this work was to compare solid lipid nanoparticles to nanostructured lipid carriers and evaluate their effect on solubility improvement and hence the bioavailability of a model insoluble drug. METHODS: Different nanosuspensions were formulated using high-speed homogenization and ultrasonication techniques, using Apifil as solid lipid and Maisine as liquid lipid. The effect of different variables on quality attributes (particle size, entrapment efficiency (EE), and in vitro release) was studied using the Box-Behnken design. Then, the optimized nanoparticles were lyophilized, filled into capsules, and evaluated. Finally, the optimized formula was clinically evaluated in six healthy human volunteers. RESULTS: It was observed that the variables had a great impact on EE and particle size. Nanoparticles showed maximum particles of 180.3 nm, and % EE ranged from 40.77% to 91.67%. Capsules loaded with NLCs were found to be more stable than those loaded with SLNs. The clinical study of NLCs-ROSCa showed an enhancement in the C max (8.92 ng/ml) compared to the commercial product (2.56 ng/ml) with approximately 349% relative bioavailability. CONCLUSION: ROSCa was successfully encapsulated in SLNs and NLCs. The optimized NLCs formulation showed improved quality attributes compared to SLNs. Thus, NLCs loaded formulations could be an effective oral drug delivery system to enhance the bioavailability of insoluble drugs.

Development of medicated chewing gum of taste masked levocetirizine dihydrochloride using different gum bases: in vitro and in vivo evaluation.

Objective: The aim of this study was to develop medicated chewing gum (MCG) formulation for taste-masked levocetirizine dihydrochloride (LCZ) that can provide fast drug release into the salivary fluid.Methods: Taste-masked LCZ was first prepared by two methods: cyclodextrin complexation using Kleptose or Captisol and formation of drug resin complex using Kyron T-154 or Kyron T-314 to overcome poor LCZ palatability. MCGs were then prepared using the taste-masked drug, gum base (Artica-T, Chicle, or Health In Gum (HIG), plasticizer (glycerol or soy lecithin at 6 or 8% of the final gum weight). The developed MCGs were evaluated for physical properties, content uniformity, and drug release. Best release MCGs were evaluated thermally to investigate the plasticizer effectiveness and for ex vivo chew out study to confirm adequate drug release. Drug bioavailability was determined for selected formula compared to commercial tablets.Results: Based on taste-masking efficiency, drug/Kleptose complex (1:3 molar ratio) was chosen for incorporation into chewing gums. Physical properties and drug release showed that gum base type, plasticizer type, and level affected not only physical properties but also drug release from MCGs. Thermal study showed decreased glass transition temperature (Tg) with increased plasticizer level. Chew out study confirmed almost complete drug release after a few minutes of chewing. Pharmacokinetic results showed shorter tmax (0.585 vs. 1.375 h) and higher Cmax (0.113 vs. 0.0765 µg/mL) for MCGs than conventional tablets.Conclusion: Results provided evidence that MCGs could be a better alternative to conventional tablet formulations with improved bioavailability and enhanced palatability.

Formulation, optimization, and evaluation of raft-forming formulations containing Nizatidine.

OBJECTIVE: The main objective of this research is to formulate, optimize, and evaluate raft-forming chewable tablets of Nizatidine. Various raft-forming agents were used in preliminary screening. Sodium alginate showed maximum raft strength, so tablets were prepared using sodium alginate as the raft forming agent, along with calcium carbonate (CaCO3) as antacid and raft strengthening agent, and sodium bicarbonate (NaHCO3) as a gas generating agent. RESEARCH DESIGN AND METHODS: Raft forming chewable tablets containing Nizatidine were prepared by direct compression and wet granulation methods, and evaluated for drug content, acid neutralization capacity, raft strength, and in-vitro drug release in 0.1 N HCl. Box-Behnken design was used for optimization. RESULTS: Two optimized formulations were predicted from the design space. The first optimized recommended concentrations of the independent variables were predicted to be X1 = 275.92 mg, X2 = 28.60 mg, and X3 = 202.14 mg for direct compression technique and the second optimized recommended concentrations were predicted to be X1 = 253.62 mg, X2 = 24.60 mg, and X3 = 201.77 mg for wet granulation technique. Optimized formulations were stable at accelerated environmental testing for six months at 35 °C and 45 °C with 75% relative humidity. X-Ray showed that the raft floated immediately after ingestion and remained intact for ∼3 h. CONCLUSION: Raft was successfully formed and optimized. Upon chewing tablets, a raft is formed on stomach content. That results in rapid relief of acid burning symptoms and delivering the drug into systemic circulation with enhanced bioavailability.