Effect of vinylpyrrolidone polymers on the solubility and supersaturation of drugs; a study using the Cheqsol method.
Eur J Pharm Sci
; 117: 227-235, 2018 May 30.
Article
em En
| MEDLINE
| ID: mdl-29481859
ABSTRACT
The development of methods to increase the bioavailability of drugs is of great interest, especially for those which are poorly soluble or permeable. One of the strategies to enhance the solubility (which in turn has the potential of increase bioavailability) of drugs is the use of additives in the formulation process, so that the drug can stay supersaturated in biological fluids for a period of time long enough to allow absorption. The use of polymers as pharmaceutical excipients in order to stabilize the supersaturation of drugs is common practice. In this work, the ability of different polymers of vinylpyrrolidone (K-12, K-17, K-25, K-29/32, K-90) and a copolymer of vinylpyrrolidone and vinylacetate (S-630) have been tested for their impact on the supersaturation of drugs. Sixteen drugs of different chemical nature have been selected, and analyzed using the Cheqsol method. The results of the drug alone, and of physical mixtures with the different polymers at several polymerdrug ratios have been compared in terms of supersaturation extent and duration. It has been observed that acidic compounds displayed enhanced solubility in different ways sometimes the supersaturated state of the drug is maintained for a long time, due to the precipitation of an amorphous solid, as determined by X-ray diffraction studies; on other occasions supersaturation increases but only for a short time, compared to the drug alone, and then the drug precipitates to a crystalline form. Only a few basic drugs displayed enhanced solubility in the presence of PVP polymers, in contrast to acidic compounds.
Palavras-chave
Bendroflumethiazide (PubChem CID: 2315); Benzthiazide (PubChem CID: 71313728); Bupivacaine hydrochloride (PubChem CID: 64737); Cyproheptadine hydrochloride (PubChem CID: 13770); Dibucaine hydrochloride (PubChem CID: 521951); Diclofenac sodium (PubChem CID: 5018304); Haloperidol (PubChem CID: 3559); Isoxicam (PubChem CID: 54677972); Ketoprofen (PubChem CID: 23684815); Maprotiline hydrochloride (PubChem CID: 71478); Olanzapine (PubChem CID: 22995473); PVP; Papaverine hydrochloride (PubChem CID: 657373); Pindolol (PubChem CID: 688095); Polyvinylpirrolidone; Propranolol hydrochloride (PubChem CID: 91536); Solubility; Supersaturation; Tetracaine (PubChem CID: 5411); Warfarin (PubChem CID: 54688261)
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Preparações Farmacêuticas
/
Povidona
/
Tecnologia Farmacêutica
/
Excipientes
Idioma:
En
Revista:
Eur J Pharm Sci
Assunto da revista:
FARMACIA
/
FARMACOLOGIA
/
QUIMICA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Espanha