Effects of Drug Particle Size and Lipid Additives on Drug Release from Paraffin Wax Formulations Prepared by Spray Congealing Technique
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Paraffin wax is a hydrophobic meltable material that can be suitably used in spray congealing to develop drug-loaded microparticles for sustained release, taste-masking or stability enhancement of drugs. However, these functional properties may be impaired if the drug particles are not completely embedded. Moreover, highly viscous melts are unsuitable for spray dispersion. In this study, the effects of drug particle size and lipid additives, namely stearic acid (SA), cetyl alcohol (CA) and cetyl esters (CE), on melt viscosity and extent of drug particles embedment were investigated. Spray congealing was conducted on the formulations, and the resultant microparticles were analysed for their size, drug content, extent of drug particles embedment and drug release. The melt viscosity increased with smaller solid inclusions while lipid additives decreased the viscosity to varying extents. The spray-congealed microparticle size was largely dependent on the viscosity. The addition of lipid additives to paraffin wax enabled more complete embedment of the drug particles. CA produced microparticles with the lowest drug release, followed by SA and CE. The addition of CA and CE enhanced the drug release and showed potential for taste-masking. Judicious choice of drug particle size and matrix materials is important for successful spray congealing to produce microparticles with the desired characteristics.
KEY WORDSparaffin wax spray congealing viscosity drug particle size lipid additives
The authors received the financial support from GEA-NUS PPRL fund (N-148-000-008-001). Ouyang Hongyi is a recipient of the National University of Singapore Graduate Research Scholarship.
- 18.Deasy PB. General introduction to microencapsulation and related drug processes. New York: M. Dekker; 1984.Google Scholar
- 34.Bodmer D, Fong JW, Kissel T, Maulding HV, Nagele O, Pearson JE, inventors; Novartis AG, assignee. Sustained release formulations of water soluble peptides. United States patent US5538739A. 1996.Google Scholar
- 47.Fischer-Tropsch waxes 2018 [cited 2018 19 March 2018]. Available from: http://www.sasolwax.com/index.php?id=fischer_tropsch_wax.
- 53.Stearic Acid [Internet]. National Center for Biotechnology Information. 2018 [cited 11 December 2018]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/stearic_acid#section=Top.
- 54.Cetyl Alcohol [Internet]. National Center for Biotechnology Information. 2018 [cited 11 December 2018]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/1-Hexadecanol#section=Top.
- 55.Cetyl Palmitate [Internet]. Royal Society of Chemistry. 2018 [cited 11 December 2018]. Available from: http://www.chemspider.com/Chemical-Structure.10427.html.
- 56.Acetaminophen [Internet]. National Center for Biotechnology Information. 2018 [cited 11 December 2018]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/acetaminophen#section=Top.
- 58.Moore JW, Flanner HH. Mathematical comparison of dissolution profiles. Pharm Technol. 1996;20(6):64–75.Google Scholar
- 60.US-FDA. Guidance for industry: dissolution testing of immediate release solid oral dosage forms. Center for Drug Evaluation and Research, Rockville; 1997a [20 April 2018].Google Scholar
- 61.Ma JKH, Hadzija B. Basic physical pharmacy. Jones & Bartlett Learning: Burlington; 2013.Google Scholar
- 65.Larkin P. Chapter 8 - illustrated IR and Raman spectra demonstrating important functional groups. Infrared and Raman spectroscopy. Oxford: Elsevier; 2011. p. 135–76.Google Scholar
- 68.Patel V, Patel NM. Controlled release of dipyridamole from floating matrices prepared using glyceryl behenate. Drug Deliv Technol. 2008;8(7):54–9.Google Scholar
- 69.Üner M, Çelebi B. Design of hydralazine hydrochloride matrix tablets based on various polymers and lipids. Ind J Pharm Edu Res. 2012;46(1):75–87.Google Scholar
- 70.Achulatla H, Rao VU, Sudhakar M. Development and study of an erodible matrix drug delivery platform for sustained release of non-steroidal anti-inflammatory drugs using melt granulation process. Open J Adv Drug Deliv. 2014;2(4):576–84.Google Scholar