Preparation and Characterization of PH-Independent Sustained-Release Tablets Containing Hot Melt Extruded Solid Dispersions of Clarithromycin : Tablets Containing Solid Dispersions of Clarithromycin

Overview

Journal AAPS PharmSciTech

Publisher Springer

Specialty Pharmacology

Date 2021 Nov 13

PMID 34773162

Citations 3

Authors

Qazi Amir Ijaz

Sumera Latif

Qurat-Ul-Ain Shoaib

Memoona Rashid

Muhammad Sohail Arshad

Amjad Hussain

Nadeem Irfan Bukhari

Sohail Riaz

Nasir Abbas

Affiliations

Soon will be listed here.

Abstract

The limited solubility of clarithromycin (CAM), coupled with low bioavailability and rapid elimination, are major shortcomings, needed to be addressed to achieve optimum therapeutic goals. Therefore, sustained-release (SR) tablets containing solid dispersion (SD) granules of CAM were prepared in this study. Initially, SD granules of CAM were prepared by hot melt extrusion (HME) technique using Kollidon VA64 as a hydrophilic carrier. The saturation solubility of SD showed almost 4.5-fold increase as compared to pure CAM in pH 6.8 medium. In vitro drug dissolution data indicated a substantial increase in the dissolution of SD as compared to that of pure CAM. The thermal stability of drug, carrier, and SD at elevated HME temperatures was evident from the results of thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Powder X-ray diffraction (PXRD) data and scanning electron microscope (SEM) images revealed a decrease in the crystallinity and the uniform dispersion of drug, respectively. Moreover, Fourier transformed infrared spectroscopy (FT-IR) data confirmed the formation of hydrogen bond between the carbonyl group of drug and the hydroxyl group of carrier. SD loaded sustained-release (SD-SR) matrix tablets were prepared with hydrophobic polymers (Eudragit RS100 and Eudragit RL100). The pH-independent swelling and permeability of both polymers were responsible for the sustained drug release from SD-SR tablets. Pharmacokinetic (PK) studies suggested a 3.4-fold increase in the relative bioavailability of SD-SR tablets as compared to that of pure CAM.

Citing Articles

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References

Shi N, Wang S, Zhang Y, Huo J, Wang L, Cai J . Hot melt extrusion technology for improved dissolution, solubility and "spring-parachute" processes of amorphous self-micellizing solid dispersions containing BCS II drugs indomethacin and fenofibrate: Profiles and mechanisms. Eur J Pharm Sci. 2019; 130:78-90. DOI: 10.1016/j.ejps.2019.01.019. View

Borba P, Pinotti M, Maduro de Campos C, Pezzini B, Stulzer H . Sodium alginate as a potential carrier in solid dispersion formulations to enhance dissolution rate and apparent water solubility of BCS II drugs. Carbohydr Polym. 2015; 137:350-359. DOI: 10.1016/j.carbpol.2015.10.070. View

Albadarin A, Potter C, Davis M, Iqbal J, Korde S, Pagire S . Development of stability-enhanced ternary solid dispersions via combinations of HPMCP and Soluplus processed by hot melt extrusion. Int J Pharm. 2017; 532(1):603-611. DOI: 10.1016/j.ijpharm.2017.09.035. View

Sotthivirat S, McKelvey C, Moser J, Rege B, Xu W, Zhang D . Development of amorphous solid dispersion formulations of a poorly water-soluble drug, MK-0364. Int J Pharm. 2013; 452(1-2):73-81. DOI: 10.1016/j.ijpharm.2013.04.037. View

Hormann T, Jager N, Funke A, Murb R, Khinast J, Paudel A . Formulation performance and processability window for manufacturing a dual-polymer amorphous solid dispersion via hot-melt extrusion and strand pelletization. Int J Pharm. 2018; 553(1-2):408-421. DOI: 10.1016/j.ijpharm.2018.10.035. View

Tran P, Lee B, Tran T . Recent studies on the processes and formulation impacts in the development of solid dispersions by hot-melt extrusion. Eur J Pharm Biopharm. 2021; 164:13-19. DOI: 10.1016/j.ejpb.2021.04.009. View

Van Snick B, Holman J, Cunningham C, Kumar A, Vercruysse J, De Beer T . Continuous direct compression as manufacturing platform for sustained release tablets. Int J Pharm. 2017; 519(1-2):390-407. DOI: 10.1016/j.ijpharm.2017.01.010. View

Krkobabic M, Medarevic D, Cvijic S, Grujic B, Ibric S . Hydrophilic excipients in digital light processing (DLP) printing of sustained release tablets: Impact on internal structure and drug dissolution rate. Int J Pharm. 2019; 572:118790. DOI: 10.1016/j.ijpharm.2019.118790. View

Yi H, Chi M, Kim Y, Woo J, Park E . Formulation of a extended release tablet containing dexibuprofen. Arch Pharm Res. 2008; 31(12):1637-43. DOI: 10.1007/s12272-001-2162-6. View

10.

Sahoo J, Murthy P, Biswal S, Manik . Formulation of sustained-release dosage form of verapamil hydrochloride by solid dispersion technique using Eudragit RLPO or Kollidon SR. AAPS PharmSciTech. 2009; 10(1):27-33. PMC: 2663666. DOI: 10.1208/s12249-008-9175-0. View

11.

Tran H, Park J, Hong K, Choi H, Han H, Lee J . Preparation and characterization of pH-independent sustained release tablet containing solid dispersion granules of a poorly water-soluble drug. Int J Pharm. 2011; 415(1-2):83-8. DOI: 10.1016/j.ijpharm.2011.05.052. View

12.

Chu S, Deaton R, Cavanaugh J . Absolute bioavailability of clarithromycin after oral administration in humans. Antimicrob Agents Chemother. 1992; 36(5):1147-50. PMC: 188854. DOI: 10.1128/AAC.36.5.1147. View

13.

Nama M, Gonugunta C, Veerareddy P . Formulation and evaluation of gastroretentive dosage forms of Clarithromycin. AAPS PharmSciTech. 2008; 9(1):231-7. PMC: 2976904. DOI: 10.1208/s12249-008-9038-8. View

14.

Szafraniec-Szczesny J, Antosik-Rogoz A, Kurek M, Gawlak K, Gorska A, Peralta S . How Does the Addition of KollidonVA64 Inhibit the Recrystallization and Improve Ezetimibe Dissolution from Amorphous Solid Dispersions?. Pharmaceutics. 2021; 13(2). PMC: 7912050. DOI: 10.3390/pharmaceutics13020147. View

15.

Das S, Das N . Preparation and in vitro dissolution profile of dual polymer (Eudragit RS100 and RL100) microparticles of diltiazem hydrochloride. J Microencapsul. 1998; 15(4):445-52. DOI: 10.3109/02652049809006871. View

16.

Smith G, Hussain A, Bukhari N, Ermolina I . Quantification of residual crystallinity in ball milled commercially sourced lactose monohydrate by thermo-analytical techniques and terahertz spectroscopy. Eur J Pharm Biopharm. 2015; 92:180-91. DOI: 10.1016/j.ejpb.2015.02.026. View

17.

Goodwin D, van den Ban S, Denham M, Barylski I . Real time release testing of tablet content and content uniformity. Int J Pharm. 2017; 537(1-2):183-192. DOI: 10.1016/j.ijpharm.2017.12.011. View

18.

Blanco M, Coello J, Gonzalez F, Iturriaga H, Maspoch S, Tomas X . Spectrophotometric determination of pharmaceutical dosages by partial least-squares calibration. J Pharm Biomed Anal. 1994; 12(4):509-14. DOI: 10.1016/0731-7085(93)e0004-7. View

19.

Zhang J, Yang W, Vo A, Feng X, Ye X, Kim D . Hydroxypropyl methylcellulose-based controlled release dosage by melt extrusion and 3D printing: Structure and drug release correlation. Carbohydr Polym. 2017; 177:49-57. PMC: 5659326. DOI: 10.1016/j.carbpol.2017.08.058. View

20.

Zhang Y, Huo M, Zhou J, Xie S . PKSolver: An add-in program for pharmacokinetic and pharmacodynamic data analysis in Microsoft Excel. Comput Methods Programs Biomed. 2010; 99(3):306-14. DOI: 10.1016/j.cmpb.2010.01.007. View