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Amelioration of physicochemical, pharmaceutical, and pharmacokinetic properties of lornoxicam by cocrystallization with a novel coformer.
- Source :
-
Drug development and industrial pharmacy [Drug Dev Ind Pharm] 2021 Mar; Vol. 47 (3), pp. 498-508. Date of Electronic Publication: 2021 Mar 01. - Publication Year :
- 2021
-
Abstract
- Objective: The present study was aimed to prepare and characterize new cocrystals of lornoxicam (LORX), a BCS class II drug employing 1,3-dimethyl urea (DMU) as a coformer to improve physicochemical, pharmaceutical, and pharmacokinetic performance.<br />Methods: A screening study was conducted by employing three techniques viz. neat grinding, liquid-assisted grinding (LAG), and solvent evaporation (SE) using different drug-coformer molar ratios (1:1, 1:2, and 1:3). Samples were characterized by DSC, PXRD, ATR-FTIR, SEM, intrinsic dissolution rate (IDR) studies, compressional studies, and pharmacokinetic studies. In vitro dissolution and stability studies (25 °C/60%RH and 40 °C/75%RH for three months) were carried out for cocrystal tablets.<br />Results: LAG and SE were found successful in ratio 1:3 and IDR showed approximately 28- and 19-fold increase, respectively in 0.1 N HCl (pH 1.2) and buffer (pH 7.4) as compared to pure LORX. The cocrystal exhibited good tabletability and was ∼2.5 times that of LORX at 6000 Psi. Dissolution profiles of tablets of cocrystal increased (56% and 100% at pH 1.2 and 7.4, respectively in contrast to those of physical mixture (PhyMix) (∼35% and ∼10%) and pure LORX (∼17% and ∼7%) within 60 min. The C <subscript>max</subscript> and AUC <subscript>0-∞</subscript> for the selected cocrystal were significantly increased ( p < 0.05) which was 2.4 and 2.5 times, respectively, that of LORX in a single dose oral pharmacokinetic study executed in rabbits. Tablets of cocrystal were found stable at both conditions.<br />Conclusion: The study indicates that cocrystallization with DMU can concomitantly improve tabletability, dissolution rate, and in vivo performance of dissolution limited drug LORX.
- Subjects :
- Animals
Crystallization
Rabbits
Solubility
Tablets
Piroxicam analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 1520-5762
- Volume :
- 47
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Drug development and industrial pharmacy
- Publication Type :
- Academic Journal
- Accession number :
- 33646919
- Full Text :
- https://doi.org/10.1080/03639045.2021.1892744