An in vitro–in vivo correlation study for nifedipine immediate release capsules administered with water, alcoholic and non-alcoholic beverages: Impact of in vitro dissolution media and hydrodynamics

Abstract

The impact of hydrodynamics and media composition on nifedipine dissolution profile from IR (immediate release) soft capsules was investigated using dissolution apparatus USP1, USP2, USP3 and USP4 (United State Pharmacopoeia). Media composition was varied in terms of pH and content, to mimic the dosage form intake with water or non-alcoholic beverages (orange juice) and alcoholic beverages (orange juice/ethanol mixture (47% v/v)). Through construction of in vitro-in vivo correlations (IVIVC) with corresponding in vivo data from the literature, it was possible to evaluate the in vitro conditions that are likely to simulate the in vivo formulation behaviour. Both linear and nonlinear correlations were obtained depending on experimental set-ups. Testing of 20mg nifedipine capsules in FaSSGFst (Fasted State Simulated Gastric Fluid pH 1.6; water administration) produced IVIVC with the USP3 (after time scaling) and USP4 apparatus. IVIVC were obtained for USP2, USP3 and USP4 in FaSSGFoj (Fasted State Simulated Gastric Fluid pH 3.4; orange juice administration). Linear and nonlinear correlations were obtained with the USP1, USP2 and USP3 apparatus when testing the capsules in FaSSGFoj/EtOH (orange juice/ethanol administration). This study highlighted that selection of physiologically relevant dissolution set-ups is critical for predicting the in vivo impact of formulations co-administration with water, non-alcoholic and alcoholic beverages.

An updated overview with simple and practical approach for developing in vitro–in vivo correlation

“…It was demonstrated that GI environment and transit time have a strong impact on in vivo dissolution and exposure of itraconazole, a class II drug (Abuhelwa, Mudge, Hayes, Upton, & Foster, ). It was disclosed that biorelevant dissolution media are important for anticipating the in vivo response of products co‐administered with aqueous and nonaqueous vehicle (Mercuri, Fares, Bresciani, & Fotaki, ). Model validation and percent predictability error (%PE) estimated for C max and AUC were held within the acceptable range (<10%) of FDA guidelines and thus proving the predictability of level A correlation for quetiapine, lidocaine, and divalproex (De Lima & De Campos, 2016; Dutta, Qiu, Samara, Cao, & Granneman, ; Kondamudi, Tirumalasetty, Malayandi, Mutalik, & Pillai, ).…”

In Vivo Predictive Dissolution Testing of Montelukast Sodium Formulations Administered with Drinks and Soft Foods to Infants

“…Understanding the dissolution profile of a pharmaceutical dosage form and linking it to its in vivo pharmacokinetic (PK) profile is a vital requirement for ensuring product quality and safety of use (1)(2)(3). Dissolution profiles can be analysed through different approaches: using modeldependent methods where experimental data are fitted using mathematical equations, model-independent methods (single values such as mean dissolution time and area under the dissolution curve (AUC) are used for data evaluation) and/or statistical methods (e.g.…”

“…The development of an IVIVC for a pharmaceutical dosage form is of great interest to the pharmaceutical industry and plays a key role in the pharmaceutical development of dosage forms (1). It can serve as a surrogate for in vivo bioavailability and be used to request biowaiver status for formulations or production changes within a product lifecycle (1)(2)(3). This reduces the need for expensive bioequivalence (BE) testing in humans.…”

Potential prediction of formulation performance in paediatric patients using biopharmaceutical tools and simulation of clinically relevant administration scenarios of nifedipine and lorazepam

“…The mini‐paddle apparatus was equipped with 200‐mL vessels and matching paddles, using a smaller volume compared to adult biorelevant studies . As intestinal motor activity matures throughout early infancy, the agitation rate of the paddle was set at 50 rotations/min.…”

“…During recent decades, the purpose of dissolution testing of drugs has expanded from pure quality control to prediction of in vivo drug performance and identifying potential bioavailability problems of pharmaceutical formulations. With development of biorelevant dissolution media (reflecting the main properties of gastrointestinal [GI] fluids), simulation of GI residence times, and simulation of GI hydrodynamics, successful in vitro–in vivo relations and correlations (IVIVRs/IVIVCs) have been established for oral immediate and modified release formulations in adults, using compendial dissolution apparatus . Furthermore, in vitro dissolution data are used as input in physiologically based pharmacokinetic (PBPK) prediction models in which different factors influencing drug absorption are integrated.…”