Co-Crystallization Approach to Enhance the Stability of Moisture-Sensitive Drugs

Abstract

Stability is an essential quality attribute of any pharmaceutical formulation. Poor stability can change the color and physical appearance of a drug, directly impacting the patient’s perception. Unstable drug products may also face loss of active pharmaceutical ingredients (APIs) and degradation, making the medicine ineffective and toxic. Moisture content is known to be the leading cause of the degradation of nearly 50% of medicinal products, leading to impurities in solid dose formulations. The polarity of the atoms in an API and the surface chemistry of API particles majorly influence the affinity towards water molecules. Moisture induces chemical reactions, including free water that has also been identified as an important factor in determining drug product stability. Among the various approaches, crystal engineering and specifically co-crystals, have a proven ability to increase the stability of moisture-sensitive APIs. Other approaches, such as changing the salt form, can lead to solubility issues, thus making the co-crystal approach more suited to enhancing hygroscopic stability. There are many reported studies where co-crystals have exhibited reduced hygroscopicity compared to pure API, thereby improving the product’s stability. In this review, the authors focus on recent updates and trends in these studies related to improving the hygroscopic stability of compounds, discuss the reasons behind the enhanced stability, and briefly discuss the screening of co-formers for moisture-sensitive drugs.

Diversity and Similarity in Isonicotinamide Two-Component Phases with Alkyl Carboxylic Acids: Focus on Solvates

“…Therefore, crystal engineering opens new opportunities to obtain APIs with better physicochemical properties. , Solvates and cocrystals often have better solubility and dissolution rate than phases formed by pure API and, therefore, increase bioavailability and drug efficacy, ,− synergistic effect, and lower the necessary drug dose, or just have more optimal properties for the manufacturing processes . Changes in the crystal form can also enhance the chemical stability of API …”

Cocrystals by Design: A Rational Coformer Selection Approach for Tackling the API Problems

“…The nature of the coformer used (acidic/basic/neutral) is known to influence the stability of the final cocrystal [1]. There have been a few instances wherein the cocrystallization technique was applied to improve the hygroscopic stability of moisture-sensitive drugs [20]. Other common instabilities such as hydrolysis, isomerization, photodegradation, etc., can also be effectively overcome by means of cocrystal preparation [21,22].…”

Multicomponent Crystals of Clozapine with Improved Solubility: A Combined Theoretical and Experimental Strategy on Coformer Screening and Structure–Property

“…The potential changes or loss of active pharmaceutical ingredients (APIs) and degradation in unstable drug products can render the medication ineffective and potentially toxic. Crystal engineering, particularly utilizing co-crystals, has demonstrated its effectiveness in improving the stability of moisture-sensitive APIs . Therefore, it is extremely important to obtain cocrystals with good humidity stability while increasing the solubility of APIs.…”

“…crystals, has demonstrated its effectiveness in improving the stability of moisture-sensitive APIs. 3 Therefore, it is extremely important to obtain cocrystals with good humidity stability while increasing the solubility of APIs. Composed of two or more components, drug multicomponent crystals (including cocrystals, salts and solvates, etc.)…”