FORMULATION AND CHARACTERIZATION OF ETHOSOMES BEARING VANCOMYCIN HYDROCHLORIDE FOR TRANSDERMAL DELIVERY

Objectives: To investigate and evaluate the transdermal delivery of ethosomes bearing vancomycin hydrochloride, a glycopeptide antibiotic with a relatively high molecular weight (1485.7Da).Methods: Vancomycin loaded ethosomes were prepared by cold method technique and characterized for vesicular shape, vesicular size, entrapment efficiency, zeta potential, in vitro drug permeation, microbiological assay against methicillin resistant Staphylococcusaureus (MRSA) and stability.Results: Microscopic examinations suggested ethosomes as unilamellar spherical vesicles. Vesicle size, entrapment efficiency and zeta potential values were depending on concentration of membrane components. Ethosomal formula having 1% phospholipid, 45% ethanol and 10% propylene glycol (F13) showed the smallest mean particle size (71.60nm±17.6) and highest transdermal flux (414.7 µg/cm2. hr) across hairless rat skin which was 72.67 times drug solution. The results obtained from microbiological assay suggested that the minimum inhibitory concentration (MIC) is affected by surface charge of ethosomes. The optimized formula on storage at 4°C for 90 days retained 89.82%±1.00 of initial drug content.Conclusions: The results collectively suggest that ethosomes are efficient carrier for transdermal delivery of vancomycin hydrochloride

DEVELOPMENT AND IN VITRO EVALUATION OF MUCOADHESIVE BILAYER BUCCAL TABLETS OF CARVEDILOL

Objectives: Carvedilol (CVD) is a nonselective β-adrenergic blocker that suffers from low absolute bioavailability (25-35%) due to first-pass metabolism. CVD-loaded buccal tablets were developed as a promising approach to overcome this limitation.Methods: The bilayers tablets were prepared by the direct compression technique. CVD-containing layer was based on one of four high molecular weight polymers; hydroxy propyl methylcellulose K15M (HPMC), Polyethylene oxide WSR N-750 (PEO), chitosan (CH) and Eudragit® RS-100 (EUD). An occlusive backing of ethylcellulose 20 (Ethocel®) was adopted as a second layer. The tablets were characterized for weight variation, thickness, friability % and drug content. Further studies were conducted to evaluate their swelling indices, surface pH, in vitro adhesion retention periods and in vitro drug release profiles.Results: The prepared tablets followed the compendial requirements for thickness, friability %, drug content and weight variation. The surface pH of all tablets ranged from 6.43 to 7.44 while their adhesion retention periods varied from 3.12 to 4.24 h. The best achieved system (PEO-based matrix; F4) displayed a reasonable adhesion retention period and a promising sustained drug release profile, over at least 8 hours, following non-fickian diffusion kinetics. This could indicate the contribution of swelling and erosion mechanisms for drug release.Conclusions: The current work succeeded in developing and evaluation of promising mucoadhesive CVD matrices suitable for buccal administration. Further pharmacokinetic and clinical studies are suggested to confirm the ability of the best achieved system to avoid the first pass metabolism of CVD and improve patient compliance.Â

Syringeable atorvastatin loaded eugenol enriched PEGylated cubosomes in-situ gel for the intra-pocket treatment of periodontitis: statistical optimization and clinical assessment

AbstractAtorvastatin calcium (ATV) is a well-known anti-hyperlipidemic drug currently being recognized for possessing an anti-inflammatory effect. Introducing it as a novel remedy for periodontitis treatment necessitates developing a syringeable modified delivery system capable of targeting inflammation within the periodontal pockets. Thus, a 33 Box-Behnken design was used to generate eugenol enriched PEGylated cubosomes. Based on the desirability function, the optimized formulation (OEEPC) was selected exhibiting a solubilization efficiency (SE%) of 97.71 ± 0.49%, particle size (PS) of 135.20 ± 1.11 nm, polydispersity index (PDI) of 0.09 ± 0.006, zeta potential (ZP) of −28.30 ± 1.84 mV and showing a sustained drug release over 12 h. It displayed a cubic structure under the transmission electron microscope, furthermore, it was stable upon storage for up to 30 days. Hence, it was loaded into an optimum syringeable in-situ gel (ISG) which displayed the desired periodontal gelation temperature (34 ± 0.70 °C) and an adequate gelation time (46 ± 2.82 sec), it also released approximately 75% of the drug within 72 h. Clinical evaluation of the ISG showed a promising percentage reduction of about 58.33% in probing depth, 90% in the bleeding index, 81.81% in the plaque index, and 70.21% in gingival levels of transforming growth factor–β1. This proved that the formulated syringeable intra-pocket delivery system of ATV is an efficient candidate for diminishing inflammation in periodontitis