Abstract
The work aimed to develop the Absorption Driven Drug Formulation (ADDF) concept, which is a new approach in formulation development to ensure that the drug product meets the expected absorption rate. The concept is built on the solubility-permeability interplay and the rate of supersaturation as the driving force of absorption. This paper presents the first case study using the ADDF concept where not only dissolution and solubility but also permeation of the drug is considered in every step of the formulation development. For that reason, parallel artificial membrane permeability assay (PAMPA) was used for excipient selection, small volume dissolution-permeation apparatus was used for testing amorphous solid dispersions (ASDs), and large volume dissolution-permeation tests were carried out to characterize the final dosage forms. The API-excipient interaction studies on PAMPA indicated differences when different fillers or surfactants were studied. These differences were then confirmed with small volume dissolution-permeation assays where the addition of Tween 80 to the ASDs decreased the flux dramatically. Also, the early indication of sorbitol’s advantage over mannitol by PAMPA has been confirmed in the investigation of the final dosage forms by large-scale dissolution-permeation tests. This difference between the fillers was observed in vivo as well. The presented case study demonstrated that the ADDF concept opens a new perspective in generic formulation development using fast and cost-effective flux-based screening methods in order to meet the bioequivalence criteria.Graphical
Highlights
During the process of formulation development for poorly water-soluble active pharmaceutical ingredients (APIs), multiple excipients and formulation strategies are tested, selected, and optimized based on stability, compatibility, safety, economic considerations, and in vivo performance
Mixed effects were experienced with fillers, where in the case of sorbitol and lactose monohydrate, a significant increase was detected, while the addition of mannitol did not impact the permeability of TEL
This paper presents the first case study using the Absorption Driven Drug Formulation (ADDF) concept: dissolution and solubility and permeability of the drug is considered in every step of the formulation development
Summary
During the process of formulation development for poorly water-soluble active pharmaceutical ingredients (APIs), multiple excipients and formulation strategies are tested, selected, and optimized based on stability, compatibility, safety, economic considerations, and in vivo performance. (e–mail: parameters to predict and control during the development process and is one of the last criteria to be tested in the form of bioequivalence study or other in vivo human clinical trials. According to the USP guideline, dissolution tests should be performed to predict the bioavailability of the drug [1, 2]. Simultaneous dissolution-permeability tests may give better in vivo predictions when studying precipitating systems [3,4,5,6]. Many important studies were published about the
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