Dissolution Enhancement and Formulation of Film Coated Tablets of Lornoxicam by Phase Transition Method: In Vitro and in Vivo Evaluation

Abstract

Objective: This study aimed to enhance the oral solubility and dissolution of poorly soluble lornoxicam by anti-solvent precipitation, and the manufacture of oral tablets by the phase transition method. 
 Methods: The solvent was mixture of polyethylene glycol 400 and absolute ethanol. Three stabilizers Inutec SP1, Pluronic F127, Sucrose ester S1670 at two concentrations and two matrix formers Mannitol, and Avicel PH102 were used to obtain 12 formulae. The formulae were characterized regarding their infrared spectroscopy (IR), differential scanning calorimetry (DSC), particle size (PS) measurement, drug content and dissolution. Further characterizations were done for the optimum formula by scanning electron microscopy (SEM) and X-ray diffraction (XRD). Four tablet formulae were manufactured by phase transition method. The optimum tablets (T3) were evaluated through hardness, drug content, disintegration, dissolution, IR, and stability studies. Finally, (T3) was compared to conventional tablets in New Zealand rabbits using crossover design.
 Results: The dissolution rate for the prepared formulae was enhanced, from 3.44 to 5.96 folds. Statistical significance was obtained using one and two way ANOVA among formulae. The optimum tablet formula (T3) had hardness 5.637±1.57 kg, drug content 90.424±1.19%, disintegration time 341.5±9.62 s and the drug dissolved 72.107±0.0025%. Stability, after one month storage of the selected tablets at (25 °c/60% relative humidity), was satisfactory. The absorption extent of lornoxicam from (T3) compared to the conventional tablets was higher.
 Conclusion: Taken together, the obtained results confirmed successfully the potential of the promising formula (T3), over the conventional tablets of lornoxicam.

A Promising Single Oral Disintegrating Tablet for Co-Delivery of Pitavastatin Calcium and Lornoxicam Using Co-Processed Excipients: Formulation, Characterization and Pharmacokinetic Study

“…Other prominent peaks appeared at 828.40 cm −1 corresponding to-CH aromatic ring bending and at 779.73 cm-1 due to C-Cl bending vibration. 30 The characteristic peaks of PITA and LORNO in the physical mixture of both drugs and the physical mixture of the M1 formula existed in their original positions without shifting, indicating the absence of incompatibility. 12 Characterization of the Single ODT Containing PITA and LORNO Table 3 reveals the outcomes of the characterization tests performed on the M1 ODT, where the obtained results met the pharmacopeial standards.…”

“…The supernatant plasma was separated and analyzed with Liquid Chromatography-Mass Spectrometry (LC-MS/ MS) (Shimadzu ® , Japan) using a previously validated LC-MS/MS method of analysis. 12,[30][31][32]…”

“…The dry residue was reconstituted in 0.5 mL of mobile phase and an aliquot of 20 µL of this solution was loaded into LC-MS/MS. 30…”

“…A non-compartmental pharmacokinetic model was used to analyze the pharmacokinetic parameters of PITA and LORNO in the M1 ODT and the marketed products using Kinetica ® software (version 5, Thermo Fisher Scientific Inc., Waltham, MA). 12,30 The values of the maximum PITA and LORNO plasma concentration (C max ) (ng/mL), the time to reach C max (T max ) (h), mean residence time…”