title: Investigating the use of liquisolid compacts technique to minimize the influence of pH variations on loratadine release.
abstract: Loratadine is a class II water-insoluble drug and its dissolution rate and, consequently, absorption are dependent on the gastrointestinal pH. The resulting very high variability in bioavailability and related inter- and intra-subject absorption variations present a major challenge that hinders the realization of an effective and uniform therapy. Among the several techniques that have been used to minimize pH dependency of dissolution rate, liquisolid compacts technique can be suggested as a promising solution. In this study, it was hypothesized that the formulation of loratadine using liquisolid compacts technique may reduce the effect of pH variation on the drug dissolution rate. Solubilities of loratadine in propylene glycol, Tween 80, and polyethylene glycol 400 were first measured and propylene glycol was selected as for producing the highest solubility among the tested solvents. Several liquisolid tablet formulations containing various ratios of drug: propylene glycol (5%, 10%, and 20% w/w) were prepared. The ratio of microcrystalline cellulose (carrier) to silica (coating powder material) was kept constant in all formulations. The dissolution behavior of loratadine from liquisolid compacts was investigated in several buffered media with different pH values (pH 1.2, 2.5, and 5). The results showed that the drug release rates produced by liquisolid compacts were significantly higher and less affected by pH variation compared with conventionally made (direct compression) and commercial (Clarityn) tablets. In conclusion, liquisolid compacts technique may be used as a tool to minimize the effects of pH variation on the dissolution rate of drugs with poor water solubility.
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Damascus University, Syria. mazenhammadi@yahoo.co.uk
authors.forename: Mazen
authors.initials: M
authors.lastname: El-Hammadi
authors.forename: Nisrine
authors.initials: N
authors.lastname: Awad
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods*; D039563:Histamine H1 Antagonists, Non-Sedating / Q000737:chemistry / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D017336:Loratadine / Q000737:chemistry* / Q000378:metabolism*; D012995:Solubility
chemical_list: D039563:Histamine H1 Antagonists, Non-Sedating; D017336:Loratadine
references.citation: Biol Pharm Bull. 2004 Oct;27(10):1630-5
references.pmid: 15467209
references.citation: Pharm Dev Technol. 2007;12(3):337-43
references.pmid: 17613897
references.citation: J Clin Pharmacol. 1987 Sep;27(9):694-8
references.pmid: 2960701
references.citation: Eur J Pharm Biopharm. 2009 Nov;73(3):373-84
references.pmid: 19679184
references.citation: Drug Dev Ind Pharm. 1999 Feb;25(2):163-8
references.pmid: 10065349
references.citation: Farmaco. 2005 Apr;60(4):361-5
references.pmid: 15848213
references.citation: Eur J Pharm Biopharm. 2008 Aug;69(3):993-1003
references.pmid: 18396390
references.citation: Colloids Surf B Biointerfaces. 2010 Aug 1;79(1):262-9
references.pmid: 20451361
references.citation: Eur J Pharmacol. 1986 Aug 7;127(1-2):153-5
references.pmid: 2875889
references.citation: J Pharm Biomed Anal. 2011 May 15;55(2):294-300
references.pmid: 21316895
references.citation: J Pharm Biomed Anal. 2008 Nov 4;48(3):1020-3
references.pmid: 18692338
references.citation: J Pharm Pharm Sci. 2005 Jan 12;8(1):18-25
references.pmid: 15946594
references.citation: Biosci Trends. 2010 Feb;4(1):17-24
references.pmid: 20305340
references.citation: J Pharm Biomed Anal. 2009 Jan 15;49(1):42-7
references.pmid: 19013045
references.citation: Int J Pharm. 2001 Jul 3;222(1):1-6
references.pmid: 11404027
references.citation: Eur J Pharm Biopharm. 2008 May;69(1):342-7
references.pmid: 17949959
references.citation: Int J Pharm. 2008 Oct 1;362(1-2):102-8
references.pmid: 18647643
references.citation: Cardiovasc Res. 1997 Aug;35(2):341-50
references.pmid: 9349397
references.citation: Pharm Res. 1992 Oct;9(10):1351-8
references.pmid: 1448438
references.citation: J Clin Pharmacol. 1996 Oct;36(10):923-30
references.pmid: 8930779