Dissolution Efficiency and Design Space for an Oral Pharmaceutical Product in Tablet Form

Abstract

8The primary drug quality requirements, safety, efficacy and reliability, for oral pharmaceutical 9 products in tablet form, translate into bioavailability, and tablet weight and strength. The 10 bioavailability of an oral drug, i.e., the amount of the drug that can reach the systemic 11 circulation, depends on drug permeation rate through the epithelial membrane or on dissolution 12 rate, in case of bioequivalence. Thus, the critical quality attributes affecting bioavailability can 13 be the dissolution profile, tablet weight and tablet hardness, which are affected by process 14 conditions and drug product composition, i.e., active pharmaceutical ingredients (APIs) and 15 excipients and their mass fractions. A Mixture Design (DOE) experiment has been carried out 16 for a generic oral drug, with input factors the mass fractions of three excipients and response 17 variables the dissolution profile, tablet weight and hardness. While the last two response 18 variables are single-point-value attributes, a dissolution profile is a multi-point-value attribute 19 and is assessed using integral measures, e.g., similarity factor, from pair-wise, model-20 independent methods. The data from the Mixture Design experiment are used to develop a multi-21 regression and multi-response optimization model, which, in turn are used to determine the 22 Design Space (DS) for the pharmaceutical product of interest. 23

Preparation and in vitro-in vivo evaluation of acyclovir floating tablets

“…where, y is the percent of drug released as a function of time, t is the total time of drug release and y100 is 100% of drug release(15). …”

An Optimization-Based Framework to Define the Probabilistic Design Space of Pharmaceutical Processes with Model Uncertainty

“…For a thorough description of the flexibility index formulation and the active-set approach, see [15,19,20]. In the subsections that follow, we will show how Equations (1)- (7) and Equations (8)-(15) can be adapted within two algorithmic frameworks to compute the probabilistic design space.…”

“…This flexibility index formulation is a direct application of Equations (1)- (7) where the process parameters θ p are treated as fixed design variables (i.e., d ≡ θ p ) and the uncertainty is captured by uncertain model parameters θ m (i.e., ϑ ≡ θ m ) as shown below Equations (16)- (23).…”

“…The final step is to run confirmatory experiments to verify the design space that will be submitted to the regulatory agency for assessment and approval. A few recent industrial applications of such a traditional method have been reported by Kumar et al (2014) [6] and Chatzizaharia and Hatziavramidis (2015) [7].…”

A Novel Framework to Aid the Development of Design Space across Multi-Unit Operation Pharmaceutical Processes—A Case Study of Panax Notoginseng Saponins Immediate Release Tablet

“…The concept of the design space is revolutionary for pharmaceutical development and improves the flexibility of pharmaceutical manufacturing. Although the design space is an optional feature of QbD approaches, its indisputable usefulness almost makes it a default feature of any QbD-based submissions [9,10,11,12,13]. To date, many studies have investigated the development of the design space.…”