FORMULATION OF ORODISPERSIBLE TABLETS CONTAINING PARACETAMOL AND THEIR IN VITRO CHARACTERIZATION – A QbD APPROACH

Abstract

Quality by Design (QbD) concept in drug formulation and development was introduced in order to achieve and ensure a proper product quality through a good process understanding. By identifying the variability sources that influence the product characteristics, the product quality can be built from the development phase. By applying this concept, in the present experimental work was intended to develop and evaluate orodispersible tablets (ODTs) with paracetamol. In order to reach a good balance between their properties: quick disintegration, convenient hardness and a fast drug release, a statistical method was used. 36 formulations were prepared according to a D-optimal experimental design. The formulation factors used in the design were: the type of the diluent agent, the type of disintegrate agent, and the percentages of the disintegrant, sweetener and flavour. The obtained tablets were analysed in vitro for their friability, disintegration time, wetting time and dissolution profile. During this experiment it was observed that the mechanical properties were mainly influenced by the type of diluent agent used, the disintegrant agent and it's ratio in each formulation. The percentage of sweetener and flavour also influenced the dissolution profile, beside the other formulation variables. QbD approach was successfully applied within this study and the ODTs with paracetamol that have desired pharmaceutical characteristics may be successfully prepared. RezumatConceptul de calitate prin design (QbD) a fost introdus în formularea şi dezvoltarea medicamentelor pentru a obţine şi a asigura o calitate adecvată produsului, având la bază o mai bună înţelegere a procesului. Calitatea produsului poate fi construită din faza de dezvoltare a acestuia, prin identificarea surselor de variabilitate care îi pot influenţa caracteristicile. Aplicând acest concept, în prezenta lucrare s-a urmărit obţinerea şi caracterizarea unor comprimate orodispersabile cu paracetamol, care să prezinte o dezagregare rapidă, o bună rezistenţă mecanică şi un profil de cedare in vitro optim. Pentru acest lucru s-au preparat 36 de tipuri de comprimate, conform unui plan experimental de optimizare. Variabilele de formulare au fost: tipul de diluant, tipul de dezagregant şi procentele de dezagregant, ȋndulcitor şi aromatizant. În vederea obţinerii unor variabile de răspuns, comprimatele au fost evaluate in vitro. Au fost evaluate friabilitatea, dezagregarea, rezistenţa mecanică, timpul de umectare şi profilul de dizolvare. Friabilitatea, dezagregarea şi rezistenţa mecanică au fost influenţate de tipul excipientului diluant folosit, de dezagregantul utilizat, dar şi de concentraţia acestuia. Profilul de dizolvare a fost influ enţat, pe lângă factorii amintiţi anterior şi de procentul de îndulcitor sintetic, dar şi de concentraţia aromatizantului. Conceptul de calitate prin design a fost aplicat cu succes acestui studiu, comprimatele orodispersabile obţinute având caracteristicile dorite.

Structural and Thermal Analysis of Cannabidiol Orodispersible Formulations

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Application of Response Surface Methodology to Optimize the Technology of Metformin Oral Dissolving Tablets

“…Fast dissolving tablets disintegrate and dissolve rapidly in the saliva, within a few seconds without drinking water or chewing [7,18]. In these cases, the bioavailability is significantly greater than the one observed with traditional solid forms such as tablets and capsules [16]. Response surface methodology (RSM) is often recommended to optimize experimental data in a multivariate system.…”

Applying the Principles of Quality by Design (Qbd) Coupled With Multivariate Data Analysis (Mvda) in Establishing the Impact of Raw Material Variability for Extended Release Tablets

“…Due to several quality assurance system failures, translated in the form of drug recalls and shortages, US FDA (United States Food and Drug Administration) started promoting new notions within the pharmaceutical professional community, like PAT (Process Analytical Technology), QbD (Quality by Design), emerging technologies (continuous manufacturing, 3D-printing), that are anticipated to enable real time control, giving a systematic understanding of products/ processes, simplifying production etc. in order to improve access to high-quality products [12,16,18,27,36,38]. The notion of QbD implies a systematic, risk based R&D (research and development) process, having as pillars the ICH guidelines: Q8 (pharmaceutical development) [22], Q9 (quality risk management) [23] and Q10 (pharmaceutical quality system) [24].…”