Preparation and in vitro-in vivo evaluation of QbD based acemetacin loaded transdermal patch formulations for rheumatic diseases.

This research aimed to develop patches for transdermal delivery of acemetacin, which can be used to treat rheumatic diseasesand to determine their potential use. Patches were successfully created by solvent casting method using hydroxypropyl methylcellulose, propylene glycol, polyethylene glycol 400, tween 80, and dimethyl sulfoxide. Prepared patches were found using the Design of Experiments (DoE) method within the Quality by Design (QbD) approach. F1-ACM with a thickness of 0.1 ± 0.0 cm, a weight of 43.33 ± 6.29 mg, pH of 4.99 ± 0.24, moisture content of 18.33 ± 2.98%, a tensile strength of 9.196 ± 0.441 Mpa, elongation at break of 28.722 ± 0.803% and drug content of 100% was chosen as ideal formulation. 89.7% of ACM from F1-ACM was released in 5 min. F1-ACM significantly (p < 0.05) increased the response latency to the thermal stimulus at 90th (3.071 ± 0.517) and 120th (3.87 ± 0.332) min in the hot plate test. In the tail-flick experiment, F1-ACM significantly (p < 0.05) increased the reaction delay against heat stimuli at 90th (3.016 ± 0.695), 120th (2.884 ± 0.851), and 180th (2.893 ± 0.932) min. F1-ACM patch significantly (p < 0.001) inhibited paw edema formation at 1, 2, 3, 4, and 5 h after induction of inflammation as compared to the control group. Therefore, this formulation can be employed more efficiently for rheumatic disease.

Preparation and Evaluation of Poly(lactic acid)/Poly(vinyl alcohol) Nanoparticles Using the Quality by Design Approach.

The aim of the study was to prepare and evaluate the potential use of poly(lactic acid)/poly(vinyl alcohol) (PLA/PVA) nanoparticle formulations as a drug delivery system. The nanoparticle formulations were successfully developed by the double emulsification/solvent evaporation method. The developed formulations were optimized using the quality by design approach of the ICH Q8 (Pharmaceutical Development) guideline. In the studies, the effects of emulsifying devices, evaporation technique, centrifugation effect, and polymer concentrations on the physicochemical parameters of the formulations were investigated to obtain the best results. Furthermore, the prepared formulations were evaluated for clarity, particle size, distribution, zeta potential, surface and morphological features, preparation efficiency, and long-term stability. Based on the obtained results, the nanoparticle formulation containing 12.5% PLA, 1% primer, and seconder PVA has a suitable particle size (181.7 ± 2.194 nm) and distribution (0.104 ± 0.049), zeta potential (-0.88 ± 0.45 mV), and high preparation efficiency (65.38%), and nanoparticles were spherical, had a smooth surface, and were stable up to 12 months. In conclusion, this novel formulation can be used as a potential drug delivery system.

Critical Tools in Tableting Research: Using Compaction Simulator and Quality by Design (QbD) to Evaluate Lubricants' Effect in Direct Compressible Formulation.

As commonly known, the product development stage is quite complex, requires intensive knowledge, and is time-consuming. The selection of the excipients with the proper functionality and their corresponding levels is critical to drug product performance. The objective of this study was to apply quality by design (QbD) principles for formulation development and to define the desired product quality profile (QTPP) and critical quality attributes (CQA) of a product. QbD is a risk- and science-based holistic approach for upgraded pharmaceutical development. In this study, Ibuprofen DC 85W was used as a model drug, Cellactose® 80 along with MicroceLac® 100 as a filler, and magnesium stearate, stearic acid, and sodium stearyl fumarate as lubricants. By applying different formulation parameters to the filler and lubricants, the QbD approach furthers the understanding of the effect of critical formulation and process parameters on CQAs and the contribution to the overall quality of the drug product. An experimental design study was conducted to determine the changes of the obtained outputs of the formulations, which were evaluated using the Modde Pro 12.1 statistical computer program that enables optimization by modeling complex relationships. The results of the optimum formulation revealed that MicroceLac® 100 was the superior filler, while magnesium stearate at 1% was the optimum lubricant. A design space that indicates the safety operation limits for the process and formulation variables was also created. This study enriches the understanding of the effect of excipients in formulation and assists in enhancing formulation design using experimental design and mathematical modeling methods in the frame of the QbD approach.

Applying Quality by Design Principles in the Development and Preparation of a New Radiopharmaceutical: Technetium-99m-Imatinib Mesylate.

The clinical impact and accessibility of 99mTc tracers for cancer diagnosis would be greatly enhanced by the availability of a new, simple, and easy labeling process and radiopharmaceuticals. In this study, Technetium-99m-imatinib mesylate ([99mTc]TcIMT) was developed and prepared as a new radiopharmaceutical for breast cancer diagnosis. The effect of critical process parameters on the product quality and stability of [99mTc]TcIMT was investigated using the quality by design concept of the ICH Q8 (Pharmaceutical Development) guideline. [99mTc]TcIMT was subjected to in vitro cell binding studies to determine healthy and cancer cell affinity using HaCaT and MCF-7 cells, respectively. The optimal radiolabeling procedure with 1 mg of IMT, 500 µg of stannous chloride, 0.1 mg of ascorbic acid, and 1mCi 99mTc radioactivity was obtained for [99mTc]TcIMT. The pH of the reaction mixture was adjusted to 10 and allowed to react for 15 min at room temperature. The radiochemical purity of [99mTc]TcIMT was found to be higher than 90% at room temperature up to 6 h. Chromatography analysis revealed >85% [99mTc]TcIMT complex formation with promising stability in saline, cell medium, and serum up to 6 h. The radiolabeled complex showed a higher cell-binding ratio to MCF-7 cells (88.90% ± 3.12) than HaCaT cells (45.64 ± 4.72) when compared to 99mTc. Our findings show that the developed preparation method for [99mTc]TcIMT falls well within the proven acceptable ranges. Applying quality by design (QbD) principles is feasible and worthwhile for the preparation of [99mTc]TcIMT. In conclusion, radiochemical purity, stability, and in vitro cell binding evaluation of the [99mTc]TcIMT complex indicate that the agent can be utilized for imaging of breast cancer cells.