QbD-enabled systematic development of gastroretentive multiple-unit microballoons of itopride hydrochloride

Abstract

The objectives of present studies were to develop the systematically optimized multiple-unit gastroretentive microballoons, i.e. hollow microspheres of itopride hydrochloride (ITH) employing quality by design (QbD)-based approach. Initially, the patient-centric QTPP and CQAs were earmarked, and preliminary studies were conducted to screen the suitable polymer, solvent, solvent ratio, pH and temperature conditions. Microspheres were prepared by non-aqueous solvent evaporation method employing Eudragit S-100. Risk assessment studies carried out by constructing Ishikawa cause-effect fish-bone diagram, and techniques like risk estimation matrix (REM) and failure mode effect analysis (FMEA) facilitated the selection of plausible factors affecting the drug product CQAs, i.e. percent yield, entrapment efficiency (EE) and percent buoyancy. A 3(3) Box-Behnken design (BBD) was employed for optimizing CMAs and CPPs selected during factor screening studies employing Taguchi design, i.e. drug-polymer ratio (X1), stirring temperature (X2) and stirring speed (X3). The hollow microspheres, as per BBD, were evaluated for EE, particle size and drug release characteristics. The optimum formulation was embarked upon using numerical desirability function yielding excellent floatation characteristics along with adequate drug release control. Drug-excipient compatibility studies employing FT-IR, DSC and powder XRD revealed absence of significant interaction among the formulation excipients. The SEM studies on the optimized formulation showed hollow and spherical nature of the prepared microspheres. In vivo X-ray imaging studies in rabbits confirmed the buoyant nature of the hollow microspheres for 8 h in the upper GI tract. In a nutshell, the current investigations report the successful development of gastroretentive floating microspheres for once-a-day administration of ITH.

Controlled release floating multiparticulates of metoprolol succinate by hot melt extrusion

“…Coated beads of calcium alginate prepared by ionotropic gelation exhibited immediate buoyancy and remained floating for prolonged periods (Iannuccelli et al, 1998). Floating microspheres of ranitidine hydrochloride (Saravanan and Anupama., 2011) verapamil hydrochloride (Streubel et al, 2002) and itopride hydrochloride (Bansal et al, 2014) were developed by solvent evaporation method, while the emulsion solvent diffusion method was effectively employed for preparation of floating microballoons which exhibited controlled release of riboflavin (Sato et al, 2003, Upadhyay et al, 2013, tranilast (Kawashima et al, 1992) and psoralen (Liu et al, 2011). Drug loaded porous calcium silicate microspheres coated with Eudragit ® S also exhibited floating and controlled release (Jain et al, 2005).…”

Systematic Development with Quality by Design Approach of Effervescent Floating Multiple Unit Minitablets of Metoprolol Succinate using Hydrophobic Grade of Gelucire

“…The first step in the risk assessment is to identify all possible risk factors which could influence the CQAs of EFMM using the Ishikawa fish-bone diagram. 27 The next step is risk analysis to screen the influential factor. FMEA is a progressive and systematic approach in order to identify the various potential failure mode associated with the product or process design.…”

QbD-Oriented Development and Characterization of Effervescent Floating-Bioadhesive Tablets of Cefuroxime Axetil

“…This confirmed gastroretentive nature of the prepared tablet formulation ostensibly owing to their floating-bioadhesive nature, which plausibly help in retaining the formulation for longer duration of time. As hypothesized, the floatation property tends to facilitate maintaining the buoyancy, while bioadhesive nature prevents dislodgment of the formulation from the gastric region even by the action of forcible house-keeping waves (6,14,37).…”