Insights into Dissolution and Solution Chemistry of Multidrug Formulations of Antihypertensive Drugs

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El Sayed, MiraUppsala universitet,Institutionen för farmaci,Recipharm OT Chemistry AB, SE-754 50 Uppsala, Sweden (författare)

Insights into Dissolution and Solution Chemistry of Multidrug Formulations of Antihypertensive Drugs

Artikel/kapitelEngelska2020

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2020-09-01
American Chemical Society (ACS),2020
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LIBRIS-ID:oai:DiVA.org:uu-421501
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-421501URI
https://doi.org/10.1021/acs.molpharmaceut.0c00835DOI

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Språk:engelska
Sammanfattning på:engelska

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Using fixed dose combinations of drugs instead of administering drugs separately can be beneficial for both patients and the health care system, but the current understanding of how multidrug formulations work at the molecular level is still in its infancy. Here, we explore dissolution, solubility, and supersaturation of various drug combinations in amorphous formulations. The effect of chemical structural similarity on combination behavior was investigated by using structurally related compounds of both drugs. The effect of polymer type on solution behavior was also evaluated using chemically diverse polymers. Indapamide (IPM) concentration decreased when combined with felodipine (FDN) or its analogues, which occurred even when the IPM solution was undersaturated. The extent of solubility decrease of FDN was less than that of IPM from the dissolution of an equimolar formulation of the drugs. No significant solubility decrease was observed for FDN at low contents of IPM which was also observed for other dihydropyridines, whereas FDN decreases at high contents of IPM. This was explained by the complex nature of the colloidal precipitates of the combinations which impacts the chemical potential of the drugs in solution at different levels. The maximum achievable concentration of FDN and IPM during dissolution of the polyvinylpyrrolidone-based amorphous solid dispersion was higher than the value measured with the hydroxypropyl methylcellulose acetate succinate-based formulation. This emphasizes the significance of molecular properties and chemical diversity of drugs and polymers on solution chemistry and solubility profiles. These findings may apply to drugs administered as a single dosage form or in separate dosage forms and hence need to be well controlled to assure effective treatments and patient safety.

Ämnesord och genrebeteckningar

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Farmaceutiska vetenskaper hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Pharmaceutical Sciences hsv//eng
amorphous
fixed dose combinations
multidrug formulations
solubility
supersaturation

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Alhalaweh, Amjad (författare)
Bergström, Christel A. S.,1973-Uppsala universitet,Institutionen för farmaci(Swepub:uu)cjo29958 (författare)
Uppsala universitetInstitutionen för farmaci (creator_code:org_t)

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Ingår i:Molecular Pharmaceutics: American Chemical Society (ACS)17:10, s. 4018-40281543-83841543-8392

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Av författaren/redakt...: El Sayed, Mira; Alhalaweh, Amjad; Bergström, Chris ...

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Av lärosätet: Uppsala universitet

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