Celecoxib (CXB) is a Biopharmaceutical Classification System (BCS) Class II molecule with high permeability that is practically insoluble in water. Because of the poor water solubility, there is a wide range of absorption and limited bioavailability following oral administration. These unfavorable properties can be improved using dry co-milling technology, which is an industrial applicable technology. The purpose of this study was to develop and optimize CXB nanoformulations prepared by dry co-milling technology, with a quality by design approach to maintain enhanced solubility, dissolution rate, and oral bioavailability. The resulting co-milled CXB composition using povidone (PVP), mannitol (MAN) and sodium lauryl sulfate (SLS) showed the maximum solubility and dissolution rate in physiologically relevant media. Potential risk factors were determined with an Ishikawa diagram, important risk factors were selected with Plackett-Burman experimental design, and CXB compositions were optimized with Central Composite design (CCD) and Bayesian optimization (BO). Physical characterization, intrinsic dissolution rate, solubility, and stability experiments were used to evaluate the optimized co-milled CXB compositions. Dissolution and permeability studies were carried out for the resulting CXB nanoformulation. Oral pharmacokinetic studies of the CXB nanoformulation and reference product were performed in rats. The results of in vitro and in vivo studies show that the CXB nanoformulations have enhanced solubility (over 4.8-fold (8.6 ± 1.06 µg/mL vs. 1.8 ± 0.33 µg/mL) in water when compared with celecoxib pure powder), and dissolution rate (at least 85% of celecoxib is dissolved in 20 min), and improved oral pharmacokinetic profile (the relative bioavailability was 145.2%, compared to that of Celebrex^®, and faster t_max 3.80 ± 2.28 h vs. 6.00 ± 3.67 h, indicating a more rapid absorption rate).

Objective: In this study, a quality-by-design (QbD) approach was used to develop a betamethasone suspension for injection formulation and to investigate the possible effects of formulation and process variables on the critical quality attributes (CQAs) of the formulation. Material and Method: It was determined that the CQAs of the formulation were particle size distribution, viscosity, sedimentation time, density and assay of active substances and preservatives, considering the quality target product profile (QTPP). Potential risk factors that may affect the CQAs of the formulation were identified using an Ishikawa diagram, and a six-factor, two-level Plackett-Burman experimental design was used to statistically investigate the effects of selected formulation and process variables. The prepared formulations were tested, and variance and multiple linear regression analyses were performed with the acquired data. Result and Discussion: As a result of the one-way analyses of variance (ANOVA) and multiple linear regression analyses, the established statistical models for the assay of methyl parahydroxybenzoate and propyl parahydroxybenzoate, and viscosity were found to be significant, the established models for other independent variables were not significant. The concentration of carmellose calcium and filter type was found to be the most significant formulation and process variables. In conclusion, this study showed that understanding the formulation and process variables that may affect the CQAs of injectable suspension formulations with a QbD approach could be useful for formulation development and optimization.

Objectives: Dexketoprofen is a non-steroidal analgesic/anti-inflammatory drug and its trometamol salt is extensively preferred in mild or moderate pain due to its rapid onset of relief. A new formulation of 36.9 mg of dexketoprofen trometamol (equivalent to 25 mg dexketoprofen) tablet has been developed and its bioequivalence to the reference product was proven. Materials and Methods: An open-label, single-dose, randomized, two-period, and cross-over bioequivalence study was conducted with healthy males under fasting conditions for two different tablet formulations of 25 mg dexketoprofen. To prove the bioequivalence of the test product with the reference product, a comparison study has been performed in compliance with regulations in force under Good Clinical Practice principles. A single-center clinical study was run and blood samples of the participants were withdrawn at specified time points, before and after dosing, to measure the plasma concentrations of dexketoprofen trometamol. A validated analytical method has been developed using an liquid chromatography with tandem mass spectrometry. Instrument to assess the plasma concentrations of the test and reference products. Results: Forty-seven volunteers completed clinical phase of the study. For the test and reference products, the mean +/- standard deviations (SD) of Cmax were found 2543.82 +/- 655.42 ng/mL and 2539.11 +/- 662.57 ng/mL, and the mean +/- SD of area under the curve (AUC) from time 0 to the last measurable concentration (AUC(0-tlast)) were found 3483.49 +/- 574.42 h.ng/mL and 3560.75 +/- 661.83 h.ng/mL, respectively. The primary target variables data demonstrate the bioequivalence of test and reference products with regard to 90% confidence interval for Cmax of 92.45-108.53% and for AUC(0-tlast)of 95.57-100.87%. The geometric mean ratios were found as 100.16% and 98.18% for Cmax and AUC(0-tlast), respectively. There were no serious adverse events or adverse reactions reported throughout the study. Conclusion: After statistical evaluation of the analytical results, the test and reference products were considered bioequivalent. Both products were well tolerated and considered as safe.

A new oral formulation of cefdinir, Cefdinir 600 mg Tablets has been developed and in this study, its relative bioavailability has been compared with another oral solid dosage form, Cefdinir 300 mg Capsules, which is already on the market. An open-label, randomized, two-period, cross-over relative bioavailability study has been conducted with healthy males under fasting conditions in compliance with Good Clinical Practice (GCP) principles. A single dose of the novel tablet formulation of 600 mg cefdinir has been compared to two doses of Cefdinir 300 mg Capsules (two capsules at once) in terms of their pharmacokinetic properties. The comparison study was performed as a single-center clinical study, and blood samples of the participants were withdrawn at specified time points, before and after dosing. The plasma concentrations and pharmacokinetic properties of two cefdinir formulations were assessed from the collected samples by using a validated LC-MS/MS analytical method. The relative bioavailability of the new formulation has been shown and both products were introduced as safe.