Polymorph Impact on the Bioavailability and Stability of Poorly Soluble Drugs

Abstract

Drugs with low water solubility are predisposed to poor and variable oral bioavailability and, therefore, to variability in clinical response, that might be overcome through an appropriate formulation of the drug. Polymorphs (anhydrous and solvate/hydrate forms) may resolve these bioavailability problems, but they can be a challenge to ensure physicochemical stability for the entire shelf life of the drug product. Since clinical failures of polymorph drugs have not been uncommon, and some of them have been entirely unexpected, the Food and Drug Administration (FDA) and the International Conference on Harmonization (ICH) has required preliminary and exhaustive screening studies to identify and characterize all the polymorph crystal forms for each drug. In the past, the polymorphism of many drugs was detected fortuitously or through manual time consuming methods; today, drug crystal engineering, in particular, combinatorial chemistry and high-throughput screening, makes it possible to easily and exhaustively identify stable polymorphic and/or hydrate/dehydrate forms of poorly soluble drugs, in order to overcome bioavailability related problems or clinical failures. This review describes the concepts involved, provides examples of drugs characterized by poor solubility for which polymorphism has proven important, outlines the state-of-the-art technologies and discusses the pertinent regulations.

A Study on the Effect of the Energy of Consciousness Healing Treatment on Physicochemical and Thermal Properties of Vitamin D<sub>3</sub> (Cholecalciferol)

“…Thus, The Trivedi Effect ® -Energy of Consciousness Healing Treatment probably introduced a polymorphic form through the energy transferred into the cholecalciferol. Polymorphic forms of pharmaceuticals have the significant effects on the drug performance, such as bioavailability, therapeutic efficacy, and toxicity, because of their thermodynamic and physicochemical properties like melting point, energy, stability, and especially solubility, are different (probably improvement) from the original form [31][32][33]. Thus, it can be predicted that Alice's Biofield Energy Treatment could be a very suitable technique for the production of novel crystal polymorph of cholecalciferol that would offer an improvement on its therapeutic performance.…”

Desafios ao controle da qualidade de medicamentos no Brasil

“…Embora alguns produtos apresentassem resultados de dissolução aceitáveis para 30 minutos, perfis de dissolução inadequados foram obtidos para a maioria deles 19 . O polimorfismo e o tamanho dos cristais do princípio ativo obtido por diferentes produtores, e mesmo entre diferentes lotes do mesmo produtor, podem ser responsabilizados por diferenças na eficácia ou na segurança de medicamentos genéricos ou similares 20,21 . Adicionalmente, a não exigência de que os ingredientes supostamente inativos nas formulações genéricas sejam idênticos aos das formulações de referência ou, ainda, a presença de diferentes impurezas pode afetar significativamente a segurança, a estabilidade e a eficácia do produto 22 .…”

Impact of Consciousness Energy Healing Treatment on the Physicochemical and Thermal Properties of Magnesium Gluconate

“…Polymorphic forms of pharmaceutical solids have the significant impact on the drug performance, such as bioavailability, therapeutic efficacy, and toxicity, because their thermodynamic and physicochemical properties like melting point, energy, stability, and especially solubility, are different (probably improvement) from the original form [39,40]. Thus, it can be anticipated that Alice's Biofield Energy Treatment could be a very useful approach for the production of novel crystal polymorph of magnesium gluconate that would provide an improvement on its therapeutic performance [41]. …”