Development of Multiple-Unit Floating Drug Delivery System of Clarithromycin: Formulation, in vitro Dissolution by Modified Dissolution Apparatus, in vivo Radiographic Studies in Human Volunteers

Abstract

Clarithromycin (CM), a broad spectrum macrolide antibiotic used to eradicate H. pylori in peptic ulcer. Clarithromycin (CM) is well absorbed from the gastrointestinal tract, but has a bioavailability of 50% due to rapid biodegradation. The aim of this investigation was to increase the gastric residence time, and to control the drug release of clarithromycin by formulating into multiple unit floating mini-tablets. Floating tablets were prepared by using direct compression method with HPMC KM and Polyox WSR 1105 as release retarded polymers and sodium bicarbonate as gas generating agent. The prepared mini-tablets were evaluated for thickness, weight variation, friability, hardness, drug content, in vitro buoyancy, swelling studies, in vitro dissolution studies by using modified Rossett-Rice test and in vivo radiographic studies in healthy human volunteers in fasting conditions. DSC analysis revealed that no interaction between drug and excipients. All the physical parameters of the tablets were within the acceptable limits. The optimized formulation (F6) had showed controlled drug release of 99.16±3.22% in 12 h, by zero-order release kinetics, along with floating lag time of 9.5±1.28 s and total floating time of 12±0.14 h. X-ray imaging studies revealed that in vivo gastric residence time of clarithromycin floating mini-tablet in the stomach was about 3.5 h. The results demonstrated that the developed floating mini-tablets of clarithromycin caused significant enhancement in gastric retention time along with sustained effect and increased oral bioavailability.

Novel Gastroretentive Floating Pulsatile Drug Delivery System Produced via Hot-Melt Extrusion and Fused Deposition Modeling 3D Printing

“…A strategy to increase the residence time of the drugs to overcome the above-mentioned drawbacks is necessary for optimal therapeutic outcomes. Numerous strategies have been used to increase the residence time of the dosage forms in the stomach, including mucoadhesive systems [8,9], high-density systems that sink to the bottom of the stomach [10], swelling systems [11] and floating systems [12][13][14]. Among these strategies, floating systems are considered superior as they do not interfere with the physiological activity of the gastrointestinal tract [15].…”

Preparation, In Vitro characterization and stability studies of ropinirole lipid nanoparticles enriched hydrogel for treatment of neurodegeneration diseases

“…RP release data were kinetically analyzed to study the possible mechanisms of drug release using Kinet DS3 software. Linear regression equations were used, and the coefficient of determination (R 2 ) was calculated 38,39 (Ref 38,39).…”

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“…Study Protocol: The in-vivo radiographic studies were carried out by administering a capsule with BaSO 4 to human volunteers and monitoring them through a radiological method 28 . Three healthy male subjects (mean age 24 years: mean weight 55 ± 10 kg) capsule was administered after taking informed consent.…”