Development of paracetamol-caffeine co-crystals to improve compressional, formulation and in vivo performance
Rattachement africain : pk, gb. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Paracetamol, a frequently used antipyretic and analgesic drug, has poor compression moldability owing to its low plasticity. In this study, new co-crystals of paracetamol (PCM) with caffeine (as a co-former) were prepared and delineated. Co-crystals exhibited improved compaction and mechanical behavior. A screening study was performed by utilizing a number of methods namely dry grinding, liquid assisted grinding (LAG), solvent evaporation (SE), and anti-solvent addition using various weight ratios of starting materials. LAG and SE were found successful in the screening study. Powders at 1:1 and 2:1 weight ratio of PCM/CAF by LAG and SE, respectively, resulted in the formation of co-crystals. Samples were characterized by PXRD, DSC, and ATR-FTIR techniques. Compressional properties of PCM and developed co-crystals were analyzed by in-die heckle model. Mean yield pressure (Py), an inverse measure of plasticity, obtained from the heckle plots decreased significantly (p < .05) for co-crystals than pure drug. Intrinsic dissolution profile of co-crystals showed up to 2.84-fold faster dissolution than PCM and physical mixtures in phosphate buffer pH 6.8 at 37 °C. In addition, co-crystals formulated into tablets by direct compression method showed better mechanical properties like hardness and tensile strength. In vitro dissolution studies on tablets also showed enhanced dissolution profiles (∼90–97%) in comparison to the tablets of PCM prepared by direct compression (∼55%) and wet granulation (∼85%) methods. In a single dose sheep model study, co-crystals showed up to twofold increase in AUC and Cmax. A significant (p < .05) decrease in clearance as compared to pure drug was also recorded. In conclusion, new co-crystals of PCM were successfully prepared with improved tabletability in vitro and in vivo profile. Enhancement in AUC and Cmax of PCM by co-crystallization might suggest the dose reduction and avoidance of side effects.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé, mais le titre doit être comparé manuellement.
- Titre Crossref
- Development of paracetamol-caffeine co-crystals to improve compressional, formulation and <i>in vivo</i> performance
- Date Crossref
- 15/02/2018
- Éditeur
- Informa UK Limited
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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University of the Punjab pays non établi dans la noticeUniversité ou école supérieure
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Bahauddin Zakariya University pays non établi dans la noticeUniversité ou école supérieure
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University of Veterinary and Animal Sciences pays non établi dans la noticeUniversité ou école supérieure
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De Montfort University pays non établi dans la noticeUniversité ou école supérieure
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University College of Pharmacy pays non établi dans la noticeUniversité ou école supérieure
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Bahaudin Zakiria University Department of Pharmacy pays non établi dans la noticeUniversité ou école supérieure
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Leicester School of Pharmacy pays non établi dans la noticeUniversité ou école supérieure
University of the Punjab, Bahauddin Zakariya University et University of Veterinary and Animal Sciences, avec 4 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.