Search results for "Dissolution testing"

Mechanistic understanding of underperforming enteric coated products: Opportunities to add clinical relevance to the dissolution test.

2020

Over the last 70 years several cases of in vivo failure of enteric coated (EC) formulations have been reported. The observed failures seem to be due to the slower than expected in vivo performance of EC products. Upon reaching the intestinal lumen, the dosage form is exposed to a bicarbonate buffered environment at much lower interfacial buffering capacity compared to those applied in compendial phosphate buffers. Hence, there is an urgent need to understand the behavior of EC products in bicarbonate buffer (BCB) and to revaluate the current dissolution methods used for such products. The current pilot study mechanistically investigated the performance of five EC products available in the C…

Improving Dissolution Behavior and Oral Absorption of Drugs with pH-Dependent Solubility Using pH Modifiers: A Physiologically Realistic Mass Transpo…

2021

Orally dosed drugs must dissolve in the gastrointestinal (GI) tract before being absorbed through the epithelial cell membrane. In vivo drug dissolution depends on the GI tract's physiological conditions such as pH, residence time, luminal buffers, intestinal motility, and transit and drug properties under fed and fasting conditions (Paixao, P. et al. Mol. Pharm. 2018 and Bermejo, et al. M. Mol. Pharm. 2018). The dissolution of an ionizable drug may benefit from manipulating in vivo variables such as the environmental pH using pH-modifying agents incorporated into the dosage form. A successful example is the use of such agents for dissolution enhancement of BCS class IIb (high-permeability,…

Viscosity-mediated negative food effect on oral absorption of poorly-permeable drugs with an absorption window in the proximal intestine: In vitro ex…

2014

Concomitant food intake can diminish oral absorption of drugs with limited permeability and an absorption window in the proximal intestine, due to viscosity-mediated decrease in dosage form disintegration time and drug dissolution rate. Three poorly-permeable drugs (atenolol, metformin hydrochloride, and furosemide) exhibiting negative food effect, and one highly-soluble and highly-permeable (metoprolol tartrate), serving as a negative control, were selected for the study. In vitro and in silico tools were used to evaluate the influence of media viscosity on drug bioperformance under fasted and fed conditions. The obtained results demonstrated that increased medium viscosity in the presence…

Relationship between particle size and dissolution rate of bulk powders and sieving characterized fractions of two qualities of orthoboric acid

1996

Drug Dev. Ind. Pharm. ISI Document Delivery No.: VN279 Times Cited: 1 Cited Reference Count: 22 Tromelin, A Habillon, S Andres, C Pourcelot, Y Chaillot, B; International audience; We have carried out a study of the particle size distribution and aqueous dissolution rate of two commercially available qualities of orthoboric acid, labeled ''crystal'' (ABC) and ''powder'' (ABP). In a previous work, we have shown that the two commercial qualities of orthoboric acid chosen as model compound (''powder'' and ''crystal'') are related to the same crystal network in spite of their different names. However, these two qualities have very different size particle distributions, as previously determined b…

Mass Transport Analysis of Bicarbonate Buffer: Effect of the CO2–H2CO3 Hydration–Dehydration Kinetics in the Fluid Boundary Layer and the Apparent Ef…

2019

The main buffering system influencing ionizable drug dissolution in the human intestinal fluid is bicarbonate-based; however, it is rarely used in routine pharmaceutical practice due to the volatility of dissolved CO2. The typical pharmaceutical buffers used fail to capture the unique aspects of the hydration-dehydration kinetics of the bicarbonate-CO2 system. In particular, CO2 is involved in a reversible interconversion with carbonic acid (H2CO3), which is the actual conjugate acid of the system, as follows CO2 + H2O ⇌ H2CO3. In contrast to ionization reactions, this interconversion does not equilibrate very rapidly compared to the diffusional processes through a typical fluid diffusion b…

Hierarchical Mass Transfer Analysis of Drug Particle Dissolution, Highlighting the Hydrodynamics, pH, Particle Size, and Buffer Effects for the Disso…

2020

Dissolution is a crucial process for the oral delivery of drug products. Before being absorbed through epithelial cell membranes to reach the systemic circulation, drugs must first dissolve in the human gastrointestinal (GI) tract. In vivo and in vitro dissolutions are complex because of their dependency upon the drug physicochemical properties, drug product, and GI physiological properties. However, an understanding of this process is critical for the development of robust drug products. To enhance our understanding of in vivo and in vitro dissolutions, a hierarchical mass transfer (HMT) model was developed that considers the drug properties, GI fluid properties, and fluid hydrodynamics. T…

2020

In this study, the potential for correlation between disintegration and dissolution performance of enteric-coated (EC) dosage forms was investigated. Different enteric hard shell capsule formulations containing caffeine as model drug were tested for disintegration (in a compendial disintegration tester) and for dissolution in both USP type I (basket) and type II (paddle) apparatuses using different media. Overall, good correlations were obtained. This was observed for both the basket and the paddle apparatus, indicating that the use of disintegration testing as a surrogate for dissolution testing (allowed by International Conference on Harmonization (ICH) for immediate release dosage forms …

Multicomponent solid dispersion as a formulation strategy to improve drug permeation: A case study on the anti-colorectal cancer irinotecan

2019

Abstract Multicomponent solid dispersions (MSD)s are frequently proposed as efficient drug delivery systems to improve drug solubility and bioavailability. In this study, the effects of specific excipients, such as mannitol, inulin, poly(methyl methacrylate-co-methacrylic)acid (PMMA) and cellulose acetate phthalate (CAP) have been tested to potentially improve irinotecan (IRN) permeation in the intestinal tract with the intention to protect the drug from the gastric environment. MSDs were formulated as microparticles by Spray-Drying technique. Raw materials and microparticles have been characterized by FTIR analysis to determine hydrogen bonding. SEM images were recorded to investigate morp…

Oral Solid Dosage Form Disintegration Testing — The Forgotten Test

2014

Since its inception in the 1930s, disintegration testing has become an important quality control (QC) test in pharmaceutical industry, and disintegration test procedures for various dosage forms have been described by the different pharmacopoeias, with harmonization among them still not quite complete. However, because of the fact that complete disintegration does not necessarily imply complete dissolution, much more research has been focused on dissolution rather than on disintegration testing. Nevertheless, owing to its simplicity, disintegration testing seems to be an attractive replacement to dissolution testing as recognized by the International Conference on Harmonization guidelines, …

Effect of thickener on disintegration, dissolution and permeability of common drug products for elderly patients

2019

Dysphagia is a very common problem suffered by elderly patients. The use of thickeners during administration in these patients helps to prevent difficulties with swallowing larger solid dosage forms. However, there are several indications when the thickeners may influence disintegration and dissolution processes of solid dosage forms, potentially affecting therapeutic efficacy. In this paper the effects of a commonly used thickener on tablet disintegration, dissolution and subsequent absorption of 6 formulated drugs frequently used in elderly patients (Aspirin, Atenolol, Acenocumarol, Candesartan, Ramipril and Valsartan) in two different administration conditions (intact tablet and crushed …