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. 2018 Jun 9;17(1):136.
doi: 10.1186/s12944-018-0783-8.

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

Madiha Maboos  1   2 , Rabia Ismail Yousuf  1 , Muhammad Harris Shoaib  3 , Iqbal Nasiri  1 , Tazeen Hussain  1 , Hafiza Fouzia Ahmed  1   2 , Wajiha Iffat  1
Affiliations

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

Madiha Maboos et al. Lipids Health Dis. .

Abstract

Background: The study was to develop an extended release (ER) encapsulated and compacted pellets of Atenolol using hydrophobic (wax based and polymeric based) and high viscosity grade hydrophilic matrix formers to control the release of this highly water soluble drug by extrusion/spheronization (ES). Atenolol is used for cardiovascular diseases and available as an immediate release (IR) tablet dosage form. The lipids, Carnauba wax (CW), Glyceryl monostearate (GMS) and cellulose based i.e. Hydroxypropyl methylcellulose (HPMC) and Ethyl cellulose (EC) were used in preparing Atenolol ER pellets. Thermal sintering and compaction techniques were also applied to control the burst release of Atenolol.

Method: For this purpose, thirty-six trial formulations (F1-F36) were designed by Response Surface Methodology (RSM), using Design-Expert 10 software, keeping (HPMC K4M, K15 M & K100 M), (EC 7FP, 10FP & 100FP), waxes (GMS, & CW), their combinations, sintering temperature and duration, as input variables. Dissolution studies were performed in pH, 1.2, 4.5 and 6.8 dissolution media. Drug release kinetics using different models such as zero order, first order, Korsmeyer-Peppas, Hixon Crowell, Baker-Lonsdale and Higuchi kinetics were studied with the help of DDsolver, an excel based add-in program.

Results: The formulations F35 and F36 showed compliance with Korsmeyer-Peppas Super case II transport model (R2 = 0.975-0.971) in dissolution medium pH 4.5. No drug excipient interaction observed by FTIR. Stereomicroscopy showed that sintered combination pellets, (F35), were highly spherical (AR = 1.061, and sphericity = 0.943). The cross-sectional SEM magnification (at 7000X) of F34 and F35 showed dense cross-linking. The results revealed that the optimized formulations were F35 (sintered pellets) and F36 (compacted pellets) effectively controlling the drug release for 12 h.

Conclusion: Extended-release encapsulated, and compacted pellets were successfully prepared after the combination of lipids CW (10%) and GMS (20%) with EC (10FP 20% & 100FP 20%). Sintering and compaction, in addition, stabilized the system and controlled the initial burst release of the drug. Extended release (ER) Atenolol is an effective alternative of IR tablets in controlling hypertension and treating other cardiovascular diseases.

Keywords: Atenolol; Carnauba wax (CW); Ethyl cellulose (EC); Extended release; Extrusion-Spheronization; Fourier transform spectroscopy (FTIR); Glyceryl monostearate (GMS); Hydroxypropyl methylcellulose (HPMC); Pellets; Scanning Electron microscopy (SEM).

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Figures

Fig. 1
Fig. 1
Perturbation and 3D plots of trial formulations (a) Release at 1st hour and (b) Aspect Ratio
Fig. 2
Fig. 2
Drug Release profile and stereomicroscopic images of cellulose based (HPMC & EC) matrix pellets
Fig. 3
Fig. 3
Release profile and stereomicroscopic images of Lipid based (GMS &CW) matrix pellets
Fig. 4
Fig. 4
Release profile, Stereomicroscopic and SEM image of combination pellets
Fig. 5
Fig. 5
Release profile, stereomicroscopic and SEM image of sintered pellets
Fig. 6
Fig. 6
Drug Release profile of F28 and F36 and SEM image of F36
Fig. 7
Fig. 7
FTIR Spectra of pure drug (a), sintered (b) and (c) Compacted Pellets
See this image and copyright information in PMC

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