Systematic Review: Cocrystal as Efforts to Improve Physicochemical and Bioavailability Properties of Oral Solid Dosage Form

Abstract

Water solubility and low bioavailability of active pharmaceutical ingredients are some of the main challenges in the process of developing new drugs, especially drugs in oral solid dosage forms. One way to improve drug solubility is the principle of cocrystallization. Cocristallyzation itself is the process of combining the active ingredients of a less water-soluble drug with a coformer so that it becomes more soluble. Pharmaceutical cocrystal provides benefits to improve physicochemical properties without affecting its pharmacological properties. In this review, we have reviewed literature discussions and research that discuss co-crystallization as an aid to improve the physicochemical and bioavailability of drugs and also discuss some drugs in the form of cocrystal and their improvement in physicochemical-biopharmaceutical properties. The main references data used in this review are research journals published in the past 10 y (2010-2020) using keywords: cocrystal, physicochemistry, bioavailability, and solid dosage form, and using google scholar as a database. Discussion on the effect of cocrystal on physicochemical properties and bioavailability of drugs was produced. The method of producing cocrystal and its characterization was also discussed. Cocrystal offers a promising approach to improve the physicochemical properties of API. The benefits of cocrystal can be observed through increased solubility, dissolution rate, permeability, bioavailability, drug stability, and tabletability.

Formulation and Evaluation of Cocrystals of a BCS Class Ii Drug Using Glycine as Coformer

“…Objective of this study was to improvise solubility of poorly water-soluble drug BCS class II drug (Ezetimibe) using cocrystal approach. Cocrystal techinque is employed as an effort to improve physicochemical properties of Ezetimibe [25]. In this regard, an attempt was made to prepare crystal engineered multicomponent form of EZE with the primary motive of enhancing its aqueous solubility.…”

Pharmaceutical Cocrystals: An Emerging Approach to Modulate Physicochemical Properties of Active Pharmaceutical Ingredients

“…[104] CODEN (USA): JDDTAO known as the supramolecular synthon. 51 These supramolecular synthons are categorized as homosynthons or heterosynthons based on the complimentary functional groups in the drug and coformer. 10 Homosynthon refers to the molecular interaction that occurs between two of the same functional groups present in the API and its coformers (such as acid-----acid and amide-----amide groups) , whereas heterosynthon refers to the interaction between two distinct functional groups.…”

“…(such as acid-----amide, acid-----pyridine and amide-----pyridine groups). 51 Hydrogen Bonding Propensity: According to numerous research, the hydrogen bond donors and acceptors of the partners should form a hydrogen bond. Furthermore, the best hydrogen bond donors and acceptors interact inside the crystal structure, resulting in the formation of co-crystals.…”

“…A crystal made up of two or more APIs (with or without the addition of a coformer) will be recognized as a drug product with a fixed-dose combination and not a single new API. 87 In 2015, EMA also published a reflection paper on the use of cocrystal from active ingredients in medicinal products. According to EMA, cocrystals are "homogeneous (single phase) crystalline structures comprising two or more components in a specific stoichiometric ratio where the arrangement in the crystal lattice is not based on ionic bonds (as with salts)".…”

X‐Ray Crystallography and Antimicrobial Activity of Synthetic Cyanoguanidinophenytoin Cocrystals

“…The hydrogen bonds can be formed due to the non‐covalent interaction between the donor groups containing nitrogen or oxygen atoms and the acceptors (hydrogen atoms). Thus, the stronger hydrogen bonds include (N−H−N), (N−H−O), (O−H−N), and (O−H−O), while the weak hydrogen bond is due to the attraction between C−H and the oxygen atom [16] . Preparations of cocrystals were categorized into two methods: i) the solvent‐based method, in which a solvent or solvent mixture is used, and it includes solvent evaporation, cooling cocrystallization, anti‐solvent addition, and slurrying [17] .…”