Lipids bearing extruded-spheronized pellets for extended release of poorly soluble antiemetic agent—Meclizine HCl

Abstract

BackgroundAntiemetic agent Meclizine HCl, widely prescribed in vertigo, is available only in immediate release dosage forms. The approved therapeutic dose and shorter elimination half-life make Meclizine HCl a potential candidate to be formulated in extended release dosage form. This study was aimed to develop extended release Meclizine HCl pellets by extrusion spheronization using natural and synthetic lipids. Influence of lipid type, drug/lipid ratio and combinations of different lipids on drug release and sphericity of pellets were evaluated.MethodsThirty two formulations were prepared with four different lipids, Glyceryl monostearate (Geleol®), Glyceryl palmitostearate (Precirol®), Glyceryl behenate (Compritol®) and Carnauba wax, utilized either alone or in combinations of drug/lipid ratio of 1:0.5–1:3. Dissolution studies were performed at variable pH and release kinetics were analyzed. Fourier transform infrared spectroscopy was conducted and no drug lipid interaction was found.ResultsSphericity indicated by shape factor (eR) varied with type and concentration of lipids: Geleol® (eR = 0.891–0.997), Precirol® (eR = 0.611–0.743), Compritol® (eR = 0.665–0.729) and Carnauba wax (eR = 0.499-0.551). Highly spherical pellets were obtained with Geleol® (Aspect ratio = 1.005–1.052) whereas irregularly shaped pellets were formed using Carnauba wax (Aspect ratio = 1.153–1.309). Drug release was effectively controlled by three different combinations of lipids: (i) Geleol® and Compritol®, (ii) Geleol® and Carnauba wax and (iii) Geleol®, Compritol® and Carnauba wax. Scanning electron microscopy of Compritol® pellets showed smooth surface with pores, whereas, irregular rough surface with hollow depressions was observed in Carnauba wax pellets. Energy dispersive spectroscopy indicated elemental composition of lipid matrix pellets. Kinetics of (i) Geleol® and Compritol® pellets, explained by Korsmeyer-Peppas (R2 = 0.978–0.993) indicated non-Fickian diffusion (n = 0.519-0.597). Combinations of (ii) Geleol® and Carnauba wax and (iii) Geleol®, Compritol® and Carnauba wax pellets followed Zero-order (R2 = 0.991–0.995). Similarity test was performed using combination of Geleol® and Compritol® (i) as a reference.ConclusionsMatrices for the extended release of Meclizine HCl from extruded-spheronized pellets were successfully formed by using three lipids (Geleol®, Compritol® and Carnauba wax) in different combinations. The encapsulated pellets of Meclizine HCl can be effectively used for treatment of motion sickness, nausea and vertigo for extended period of time.

Effect of lipid and cellulose based matrix former on the release of highly soluble drug from extruded/spheronized, sintered and compacted pellets

“…The sphericity of pellets also became poor and irregular with CW [ 58 ]. Faaiza et al reported that the CW is the best release retarding agent for poorly soluble drug- Meclizine HCl due to the absence of pores but destruct the morphology of pellets [ 59 ]. While, previously reported studies showed that the release of theophylline was retarded up to 3 h only and showed burst release was found even when CW was used in higher concentrations [ 4 , 15 ].…”

“…Only some additional peaks were observed before the spectra of Atenolol, might be associated with the different composition of CW. A researcher has also reported extra peaks of aluminum, copper, and zinc, in CW spectrum, due to its vegetable origin [ 59 ].…”

QbD based Eudragit coated Meclizine HCl immediate and extended release multiparticulates: formulation, characterization and pharmacokinetic evaluation using HPLC-Fluorescence detection method

“…Flow properties of both immediate and coated pellets were determined by evaluating bulk density, tapped density, compressibility index, Hausner ratio, and angle of repose "α". These parameters were calculated using the following equations (1) where M is the mass of pellets, V o and V f are the bulk and tapped volumes of pellets respectively. Compressibility index 11-15 and Hausner ratio 1.12-1.18 show good flow properties, whereas, compressibility index ≤ 10 and Hausner ratio 1.00-1.11 exhibit excellent flow properties.…”

“…It is a non-destructive technique in which pellets and their cross-sections were bombarded with an electron beam, resulting in the emission of X-rays that are specific to each element. These emitted X-rays were detected by X-ray spectrometer 1 .…”

“…Therefore, its solubility and ionization are reduced at alkaline pH and increased at acidic pH. This may be due to the conversion of the hydrochloride salt to its less soluble free base 1 . Meclizine HCl release was decreased as the pH was increased from 1.2 to 6.8.…”