In Vitro Dissolution and Permeability Testing of Inhalation Products: Challenges and Advances

Abstract

In vitro dissolution and permeability testing aid the simulation of the in vivo behavior of inhalation drug products. Although the regulatory bodies have specific guidelines for the dissolution of orally administered dosage forms (e.g., tablets and capsules), this is not the case for orally inhaled formulations, as there is no commonly accepted test for assessing their dissolution pattern. Up until a few years ago, there was no consensus that assessing the dissolution of orally inhaled drugs is a key factor in the assessment of orally inhaled products. With the advancement of research in the field of dissolution methods for orally inhaled products and a focus on systemic delivery of new, poorly water-soluble drugs at higher therapeutic doses, an evaluation of dissolution kinetics is proving crucial. Dissolution and permeability testing can determine the differences between the developed formulations and the innovator’s formulations and serve as a useful tool in correlating in vitro and in vivo studies. The current review highlights recent advances in the dissolution and permeability testing of inhalation products and their limitations, including recent cell-based technology. Although a few new dissolution and permeability testing methods have been established that have varying degrees of complexity, none have emerged as the standard method of choice. The review discusses the challenges of establishing methods that can closely simulate the in vivo absorption of drugs. It provides practical insights into method development for various dissolution testing scenarios and challenges with dose collection and particle deposition from inhalation devices for dissolution tests. Furthermore, dissolution kinetic models and statistical tests to compare the dissolution profiles of test and reference products are discussed.

A Novel Combined Dry Powder Inhaler Comprising Nanosized Ketoprofen-Embedded Mannitol-Coated Microparticles for Pulmonary Inflammations: Development, In Vitro–In Silico Characterization, and Cell Line Evaluation

“…As mentioned previously, KETO is a poorly water-soluble drug, and its release profile is shown in Figure 6 . It is known in pulmonary delivery that the delivered medication dose must be quickly dissolved and released upon lung deposition to reduce the risk of a clearance mechanism (i.e., macrophage uptake) [ 38 , 58 ]. It is demonstrated that ~80% of the drug released from our formulations within the first 5 min, while only 11% released from the raw KETO.…”

“…Accordingly, a fast dissolution rate was achieved, in which 80% of the drug was released in 10 min due to the nanosize of the ketoprofen. In order to lower the chance of clearance mechanisms, it is well established in pulmonary administration that the administered drug needs to be rapidly dissolved and released upon lung deposition [ 38 , 58 ]. Moreover, all samples showed a significant anti-inflammatory effect and decreased IL-6 on the LPS-treated U937 cell line, with low toxicity indicating their safety.…”

Carrier-Free Inhalable Dry Microparticles of Celecoxib: Use of the Electrospraying Technique

“…The importance of the dissolution of orally inhaled drug formulations in DPIs was highlighted by Nokhodchi et al [ 43 ]. Pulmonary drug absorption and, consequently, clinical performance, might be limited by the dissolution or release processes.…”

Green Routes for Bio-Fabrication in Biomedical and Pharmaceutical Applications

“…The solubility and poor solubility of the molecules determine the variation in classification. In particular, in vitro dissolution studies or in vivo permeations studies have been carried out [ 101 ]. Specifically, using these drugs that are produced using safe methods is always of great environmental interest.…”