title: Optimization of storage and manufacture conditions for imidapril hydrochloride in solid state as a way to reduce costs of antihypertensive therapy.
abstract: The effect of temperature and relative humidity (RH) on the stability of imidapril hydrochloride (IMD) in solid state was investigated. The main aim of this study was to determine the most appropriate conditions of storage and manufacture of IMD so that the efficiency of the technological process could be improved and its costs could be minimized. A reversed-phase high-performance liquid chromatography was validated and applied for the determination of IMD degradation samples under the following operating conditions: stationary phase, LiChrospher 100 RP-18 (size 5 μm) 250 × 4 mm I.D., and mobile phase, acetonitrile-methanol-phosphate buffer, pH 2.0, 0.035 mol L(-1) (60:10:30 v/v/v). The effect of temperature on IMD degradation rate was analyzed under increased RH ≈ 76.4% (within temperature range of 70-90°C) and decreased RH ≈ 0% (within temperature range of 90-110°C). The influence of RH was investigated under 90°C within RH range of 25.0-76.4%. IMD degradation accords with autocatalytic reaction model, and RH has no influence on its mechanism yet it increases its rate. The reaction also accelerates under high temperatures and in the presence of IMD degradation product. Pure IMD is more stable than other structurally related angiotensin-converting enzyme inhibitors, such as enalapril maleate, but it still should be stored in tightly closed containers and protected from moisture and high temperatures.
authors.affiliation: The Oncology Center of Wielkopolska, 15 Garbary Str., 61-866, Poznan, Poland. katarzyna.regulska@wco.pl
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Regulska
authors.forename: Beata
authors.initials: B
authors.lastname: Stanisz
authors.forename: Paweł
authors.initials: P
authors.lastname: Lisiecki
mesh_terms: D000959:Antihypertensive Agents / Q000737:chemistry* / Q000627:therapeutic use; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D048289:Imidazolidines / Q000737:chemistry* / Q000627:therapeutic use; D010316:Particle Size; D015203:Reproducibility of Results; D013696:Temperature
chemical_list: D000959:Antihypertensive Agents; D048289:Imidazolidines; C065166:imidapril
references.citation: J Pharm Biomed Anal. 1996 Jan;14(3):281-7
references.pmid: 8851752
references.citation: Drug Dev Ind Pharm. 2013 Jan;39(1):51-61
references.pmid: 22348774
references.citation: J Phys Chem B. 2006 Sep 7;110(35):17315-28
references.pmid: 16942065
references.citation: Acta Pol Pharm. 2004 Mar-Apr;61(2):91-6
references.pmid: 15493289
references.citation: Acta Pol Pharm. 2011 Sep-Oct;68(5):645-51
references.pmid: 21928708
references.citation: J Chromatogr. 1992 Oct 2;581(1):65-73
references.pmid: 1430009
references.citation: Pharmazie. 2003 Apr;58(4):249-51
references.pmid: 12749406
references.citation: Acta Pol Pharm. 2003 Nov-Dec;60(6):443-9
references.pmid: 15080591
references.citation: J Hypertens Suppl. 1995 Sep;13(3):523-30
references.pmid: 8592249
references.citation: J Pharm Biomed Anal. 2003 Feb 26;31(2):375-80
references.pmid: 12609677
references.citation: Curr Pharm Des. 2007;13(13):1335-45
references.pmid: 17506719