Formulation development of anti-stress compressed lozenges using a fractional factorial Latin cube design and ANOVA approach

The aim of this work was to develop anti-stress compressed lozenges containing 100 mg of glycine and 250 mg of magnesium citrate obtained by the direct compression method. To choose optimal excipient composition providing the sufficient pharmaco-technical properties of the tablet blend, mechanical strength of tablets and non-disintegrating, slow-dissolving behavior of compressed lozenges during sucking, 27 experimental formulations according to fractional factorial Latin cube design were prepared and tested. The excipients used in the study were: Mannogem® EZ, Cellactose® 80 and GalenIQ™ 721 (fillers); Plasdone™ S-630, Kollidon® 90 F and Avicel® PH-101 (dry binders); Metolose® 90SH-4000SR and guar gum (gel-forming binders); PRUV®, Neusilin® US2, and Compritol® 888 CG ATO (antifriction excipients). The following parameters were investigated as responses: bulk density, Carr’s index, friability, resistance to crushing, and in vitro disintegration time. ANOVA approach was applied for statistical processing, which allowed to reveal the individual effects of each excipient and several interaction effects observed for the excipient amounts used in this study. Isomalt (GalenIQ™ 721), copovidone (Plasdone™ S-630), and glyceryl behenate (Compritol® 888 CG ATO) were selected to be incorporated in the final formulation of compressed lozenges.

Design of Caffeine-Loaded Nanostructured Lipid Carriers Containing Coconut Oil for Topical Application

Although caffeine was suggested as one of the pharmacological agents for the cellulite treatment, its skin permeation restricted. The present work was aimed at formulating caffeine loaded nanostructured lipid carriers (CAF-NLCs) containing coconut oil as a topical delivery system. CAF-NLCs were prepared by the ultrasonic emulsification method, using coconut oil as a liquid lipid. The proper selection of solid lipid and surfactants for these formulations were investigated. Subsequently, physicochemical properties, entrapment efficacy, stability, and in vitro drug release were evaluated. The CAF-NLCs containing coconut oil was successfully prepared using glyceryl behenate as a solid lipid and showed an interesting entrapment efficiency (62-99%). The obtained CAF-NLCs presented the nanosized range (≈ 60-390 nm), with a low polydispersity index and high negative zeta potential values (over ‐30 mV). However, the type and concentration of surfactant also affected these properties. These results suggested that CAF-NLCs containing coconut oil are the promising carrier for delivery of caffeine following topical application.

Multilayer-Coated Tablet of Clopidogrel and Rosuvastatin: Preparation and In Vitro/In vivo Characterization

The acid lability of rosuvastatin hinders the preparation of mixed combination formulations of rosuvastatin with acidic drugs such as clopidogrel. Therefore, the purpose of this study was to develop a multilayer-coated tablet that avoids physicochemical interactions between rosuvastatin and clopidogrel. Among the tested hydrophobic materials, glyceryl behenate was most effective at inhibiting the production of lactone, the acid degradation product of rosuvastatin. Therefore, the multilayer-coated tablet included a hydrophobic separation layer consisting of glyceryl behenate between the clopidogrel core tablet and the rosuvastatin coating layer. In order to prevent delayed dissolution by the stable hydrophobic separation layer, crospovidone was added into the clopidogrel core tablet as an effective disintegrant. Copovidone was also added to the coating layer of rosuvastatin, achieving a dissolution profile comparable to that of the reference drug, Crestor®. The resulting multilayer-coated tablet exhibited similar pharmacokinetic profiles to those of reference drugs (Plavix® and Crestor®) in beagle dogs, and there was no statistically significant difference in the maximum plasma concentration (Cmax), the time to reach the maximum plasma concentration (Tmax), or the area under the plasma-concentration time curve (AUC) between the test and reference formulations. The storage stability tests showed that the amounts of acid degradation products and total impurities were comparable to that of the reference drug. In conclusion, the present study successfully developed a stable multilayer-coated tablet containing both clopidogrel and rosuvastatin that may improve the patient compliance in combination therapy for cardiovascular diseases.