Leveraging Dissolution by Autoinjector Designs

Int J Cur Biomed Phar Res, 2011

Journal of Pharmaceutical Sciences, 1999

Dissolution test is required to study the drug release from the dosage form and its in vivo performance. Dissolution test is used to asses the lot to lot quality of drug product. The development and validation of dissolution procedures is of paramount importance during development of new formulation and in quality control. The dissolution procedure must be properly developed and validated. The objective of this paper is to review the development and validation of dissolution procedure(s) and to provide practical approaches for determining specificity, linearity, range, accuracy, precision, limit of detection, limit of quantitation and robustness of methods. Developing and validating dissolution test procedures can be a challenging process, on multiple fronts. Methods must be developed and validated not just for the dissolution test procedure itself, but also for any assay used to evaluate the test results. INTRODUCTION The dissolution test is required for various dosage forms for product release testing. It is also commonly used as a predictor of the in vivo performance of a drug product. To satisfy dissolution requirements, the USP provides information in the way of a general chapter on dissolution, as well as related chapters on disintegration and drug release (USP 32-NF 27, 2009). The USP and FDA also provide guidelines on development and validation of dissolution procedures (USP 32-NF 27, 2009; ICH guideline, 2005; Guidance for Industry 1997, 2000) and while this white paper will draw from this information and will discuss the available guidance in some detail, the reader is encouraged to consult the reference for additional details. In vitro dissolution data, together with bioavaibility and chemistry, manufacturing and control data, is a critical component of any new drug application (NDA) submitted to the FDA. A dissolution test is really a simple concept; a tablet or capsule is placed into a known volume of media and as it dissolves the resulting solution is sampled over time, and assayed (often by HPLC or by spectrophotometry) for the level of active pharmaceutical ingredient (API) present. However, the design, development, and the validation of the procedure can be quite involved, especially when one considers that not only the dissolution procedure must be developed and validated, but also any analytical technique used for the assay.

Dissolution Technologies

Quality control dissolution testing represents a key product performance test for solid oral dosage forms and is the most likely QC test to result in laboratory investigations because of the relatively complex relationship between the dissolution performance, the drug product properties, and the systems necessary to measure the quality attribute. The Dissolution Working Group of the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) has pooled our collective knowledge to outline some common ways that dissolution methods can fail. Examples and case studies are given to highlight errors related to equipment, method, materials, measurement, people, and the environment. Best practices for building method understanding and avoiding the exemplified issues are discussed. Case studies highlight the importance of buffer preparation, potential impact of contamination of the dissolution medium, additive-induced degradation, risks in the use of automation, differences between dissolution systems, and the effect of filter selection. Investing in analyst training programs, understanding the capabilities of your equipment portfolio, and using well-designed studies for robustness and ruggedness will reduce dissolution method investigations and improve compliance and productivity during the method lifecycle.

Dissolution Technologies, 2013

The selection of media in dissolution method development can sometimes be an arbitrary decision. The case studies in this article give a practical rationale that should help in selecting media, especially surfactants. Three cases were studied: (1) the role of surfactants versus compound stability in the dissolution medium during dissolution method development, (2) the selection of a surfactant based on interactions between the dissolution medium and the drug substance, and (3) the selection of media based on formulation properties. In the first case study, the choice of surfactant in relation to solubility and physical stability of the drug substance is shown. The second revealed an unexpected synergy between polysorbate 20 (Tween) and acetic acid solution that caused an unusual increase in the dissolution rate compared with these media used separately. In the last case study, the medium was modified by addition of surfactant to reflect a change in the formulation. The selection of a dissolution medium should be based on drug substance and formulation characteristics as well as on interactions among components.

2004

ECF 15 - The 15th European Conference of Fracture - advanced fracture mechanics for life and safety assessments, Stockholm, August 11-13, 2004

Dissolution Technologies, 2016

This study describes various complications related to sample preparation (filtration) during development of a dissolution method intended to discriminate among different fenofibrate immediate-release formulations. Several dissolution apparatus and sample preparation techniques were tested. The flow-through cell apparatus (USP 4) was found unfit for dissolution testing of fenofibrate MeltDose formulations due to clogging of filters and varying flow rates. A mini paddle dissolution setup produced dissolution profiles of the tested formulations that correlated well with clinical data. The work towards the mini paddle dissolution method demonstrates that sample preparation influenced the results. The investigations show that excipients from the formulations directly affected the drug-filter interaction, thereby affecting the dissolution profiles and the ability to predict the in vivo data. With the tested drug-formulation combination, the best in vivo-in vitro correlation was found after filtration of the dissolution samples through 0.45-µm hydrophobic PTFE membrane filters.

Journal of Pharmacy and Pharmacology, 2002

The aim of the present study was to determine the apparent diffusion boundary layer and dissolution rate constant for various surfaces of compacts and at various locations in the USP paddle dissolution apparatus. Benzoic acid compacts were coated with paraf n wax leaving only the surface under investigation free for dissolution. The dissolution rates for various surfaces at varying locations in the paddle dissolution vessel were determined from the slope of the dissolution pro le (amount dissolved (mg) versus time (min)). The apparent diffusion boundary layer and dissolution rate constant were calculated and were found to vary depending on the surface of the compact from which dissolution took place and also on the location and size of the compact. It may be concluded that, in developing models to describe the dissolution from solid dosage forms, it is not accurate to assume constant hydrodynamics and mass transfer rates at all surfaces of the system, or in different locations within the test device. A more exact description of the hydrodynamics would be necessary in order to precisely model drug dissolution in the paddle dissolution apparatus.

Journal of Pharmaceutical Sciences, 2018

The hydrodynamics of a miniaturized dissolution apparatus was characterized using computational fluid dynamics (CFD) simulations and analyzed in relation to the biorelevance and robustness of measurements of drug dissolution and precipitation kinetics from supersaturated drug solutions. The effect of using three different agitator geometries operated at 50, 100, 150 and 200 RPM as well as different positioning of an UV probe in the vessel was systematically evaluated. The CFD simulations were validated using a particle streak velocimetry experiment. The results show that the choice of agitator geometry influences the hydrodynamics of the system and indicates that an off-center probe position may result in more robust measurements. Furthermore, the study shows that the agitator geometry has a significant effect on supersaturation studies due to differences in the hydrodynamic shear produced by the agitator.