Evaluation of the compression properties of co-processed paracetamol, gelatin and microcrystalline cellulose formulation prepared via melt-in agglomeration

Document Type : Original Article


1 Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, Igbinedion University, Okada, Edo State, Nigeria.

2 Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, University of Benin, Benin City, Edo State, Nigeria.


Co-processing techniques have been used to modify the properties of dosage forms. The aim of this study is to evaluate the granules and tablet properties of co-processed paracetamol, gelatin and microcrystalline cellulose. Batches of co-processed paracetamol granules (A-E) were prepared by melt-in agglomeration process using paracetamol with varying amounts of gelatin (1.0, 2.0, 3.0 or 4.0 % w/w) or starch (3.0 % w/w) and microcrystalline cellulose. A control batch (F) of conventional granules was also prepared by wet granulation method with starch mucilage (4.0 % w/w). The granules were subjected to micromeritic, compaction and differential scanning calorimetric analyses. The granules were compressed into tablets and their tablet properties evaluated. Granules of batches A-D had higher percent maximum volume reduction of 12.25-16.13 % compared to the percent maximum volume-reduction (9.52 and 11.81) of granules from batches E and F respectively. Differential scanning result indicates amorphous solidification of co-processed paracetamol. Tablets formulated from batches A-D showed improve tensile strength (3.63 - 8.26 Nm-2) and faster disintegration time (1.32- 1.12 min) compared to the tensile strengths (5.09 & 5.01 Nm-2) and disintegration times (2.54 & 4.43 min) of tablets from batches E and F respectively. There were no significant difference (P≥0.05) in their maximum amounts ( >70 %) of drug released after 40 min. Melt-in agglomeration of paracetamol and gelatin with microcrystalline cellulose created amorphous dispersion that improved tabletability parameters of granules and disintegration time and dissolution properties of tablets.


1.    Ilić I, Kása P Jr, Dreu R, Pintye-Hódi K, Srcic S. The compressibility and compactibility of different types of lactose. Drug Dev Ind Pharm. 2009 Oct;35(10):1271-80. doi: 10.1080/03639040902932945. PMID: 19466896.
2.    Conceicao J, Estanquerio M, Amara MH, Silva JP, Sousa-Lobo JM. Technological excipients of tablets: study of flow properties and compaction behaviour. Am J Med Sci Medicine. 2014;2(4);71-76. Doi: 10.12691/ajmsm-2-4-2
3.    Cabiscol R, Shi H, Wunsch I, Magnanimo V, Finke JH, Luding S, Kwade A. Effect of particle size on powder compaction and tablet strength using limestone. Adv Powder Technology. 2020;31(3):1280-9.
4.    Khan KU, Minhas MU, Badshah SF, Suhail M, Ahmad A, Ijaz S. Overview of nanoparticulate strategies for solubility enhancement of poorly soluble drugs. Life Sci. 2022 Feb 15;291:120301. doi: 10.1016/j.lfs.2022.120301. Epub 2022 Jan 6. PMID: 34999114.
5.    Dannenfelser RM, He H, Joshi Y, Bateman S, Serajuddin AT. Development of clinical dosage forms for a poorly water soluble drug I: Application of polyethylene glycol-polysorbate 80 solid dispersion carrier system. J Pharm Sci. 2004 May;93(5):1165-75. doi: 10.1002/jps.20044. PMID: 15067693.
6.    Miller DA, McConville JT, Yang W, Williams RO 3rd, McGinity JW. Hot-melt extrusion for enhanced delivery of drug particles. J Pharm Sci. 2007 Feb;96(2):361-76. doi: 10.1002/jps.20806. PMID: 17075869.
7.    Saritha D, Bose PSC, Reddy PS, Madhuri G, Nagaraju R. Improved dissolution and micromeritic properties of naproxen from spherical agglomerates: preparation, in vitro and in vivo characterization. Braz J Pharm Sci. 2012;48(4):667-676.x
8.    Vilhelmsen T, Eliasen H, Schaefer T. Effect of a melt agglomeration process on agglomerates containing solid dispersions. Int J Pharm. 2005 Oct 13;303(1-2):132-42. doi: 10.1016/j.ijpharm.2005.07.012. PMID: 16139973.
9.    Sinha S, Ali M, Baboota S, Ahuja A, Kumar A, Ali J. Solid dispersion as an approach for bioavailability enhancement of poorly water-soluble drug ritonavir. AAPS PharmSciTech. 2010 Jun;11(2):518-27. doi: 10.1208/s12249-010-9404-1. Epub 2010 Mar 18. PMID: 20238187; PMCID: PMC2902348.
10.    Tantishaiyakul V, Kaewnopparat N, Ingkatawornwong S. Properties of solid dispersions of piroxicam in polyvinylpyrrolidone. Int J Pharm. 1999 Apr 30;181(2):143-51. doi: 10.1016/s0378-5173(99)00070-8. PMID: 10370210.
11.    Ogunjimi AT, Alebiowu G. Neem gum as a binder in a formulated paracetamol tablet with reference to Acacia gum BP. AAPS PharmSciTech. 2014 Apr;15(2):500-10. doi: 10.1208/s12249-014-0079-x. Epub 2014 Feb 6. PMID: 24500339; PMCID: PMC3969499.
12.    Persson AS, Ahmed H, Velaga S, Alderborn G. Powder Compression Properties of Paracetamol, Paracetamol Hydrochloride, and Paracetamol Cocrystals and Coformers. J Pharm Sci. 2018 Jul;107(7):1920-1927. doi: 10.1016/j.xphs.2018.03.020. Epub 2018 Mar 31. PMID: 29614273.
13.    Tranová T, Pyteraf J, Kurek M, Jamróz W, Brniak W, Spálovská D, Loskot J, Jurkiewicz K, Grelska J, Kramarczyk D, Mužíková J, Paluch M, Jachowicz R. Fused Deposition Modeling as a Possible Approach for the Preparation of Orodispersible Tablets. Pharmaceuticals (Basel). 2022 Jan 5;15(1):69. doi: 10.3390/ph15010069. PMID: 35056125; PMCID: PMC8781976.
14.    Okoye EI, Onyekweli AO, Ohwoavworhua FO, Kunle OO. Comparative study of some mechanical and release properties of paracetamol tablets formulated with cashew tree gum, povidone and gelatin binders. Afr J Biotechnol. 2009;8(16): 3970-3 
15.    Persson AS, Pazesh S, Alderborn G. Tabletability and compactibility of α-lactose monohydrate powders of different particle size. I. Experimental comparison. Pharm Dev Technol. 2022 Mar;27(3):319-330. doi: 10.1080/10837450.2022.2051550. Epub 2022 Mar 23. PMID: 35285375.
16.    Ogunjimi AT, Alebiowu G. Flow and consolidation properties of Neem gum co-processed with two pharmaceutical excipients. Powder Technol. 2012; 246: 187-192. Doi: 10.1016/j.powtec.2013.04.051.
17.    Choi DH, Kim NA, Chu KR, Jung YJ, Yoon J-H, Jeong H. Material properties and compressibility using Heckel and Kawakita equation with commonly used pharmaceutical excipients. J Pharm Investig. 2010;40(4): 237-244.
18.    Rashid I, Haddadin RR, Alkafaween AA, Alkaraki RN, Alkasasbeh RM. Understanding the implication of Kawakita model parameters using in-die force-displacement curve analysis for compacted and non-compacted API powder. AAPS Open. 2022;8(6). 
19.    Castellanos A. The relationship between attractive interparticle forces and behaviour in dry and uncharged fine powders. Adv Physics. 2005;54(4):263-376. 
20.    Nordstrom J, Welch K, Frenning G, Alderborn G. On the physical interpretation of the Kwakita and Adams parameters derived from confined compression of granular solids. Powder Technol. 2008;182(3): 424-435.
21.    Nordström J, Klevan I, Alderborn G. A particle rearrangement index based on the Kawakita powder compression equation. J Pharm Sci. 2009 Mar;98(3):1053-63. doi: 10.1002/jps.21488. PMID: 18704952. 
22.    Bejaoui M, Ouslati H, Galai H. Ternary Solid Dispersion Strategy for Solubility Enhancement of Poorly Soluble Drugs by Co-Milling Technique. In: Berrada M., editor. Chitin and Chitosa n-Physicochemical Properties and Industrial Applications [Internet]. London: IntechOpen; 2021 [cited 2022 Sep 3]. Available from: https://www.intechopen.com/chapters/755105 doi: 10.5772/intechopen.95518
23.    Granberg RA, Rasmuson AC. Solubility of paracetamol in pure solvents. J Chem Eng Data 1999;14:1391-5