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- Title
Development of paracetamol-caffeine co-crystals to improve compressional, formulation and in vivo performance.
- Authors
Latif, Sumera; Abbas, Nasir; Hussain, Amjad; Arshad, Muhammad Sohail; Bukhari, Nadeem Irfan; Afzal, Hafsa; Riffat, Sualeha; Ahmad, Zeeshan
- Abstract
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 C max . 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 C max of PCM by co-crystallization might suggest the dose reduction and avoidance of side effects.
- Publication
Drug development and industrial pharmacy, 2018, Vol 44, Issue 7, p1099
- ISSN
1520-5762
- Publication type
Journal Article
- DOI
10.1080/03639045.2018.1435687