Pharmaceutical Cocrystals: A Novel Approach for Oral Bioavailability Enhancement of Drugs

Abstract

Solid dosage forms are by far the preferred drug delivery systems. However, these often face the problem of poor and erratic bioavailability during the drug development process. Numerous formulation strategies for drug delivery are currently under development, among which the solid forms such as polymorphs, solvates, salts, and cocrystals have been considered to be the most important for improving dissolution rate and bioavailability. Cocrystallization is a fairly new approach in pharmaceutical industry that can improve the solubility and, consequently, the bioactivity of the active pharmaceutical ingredient (API) without compromising its structural integrity. Pharmaceutical cocrystals have found their place in drug delivery, primarily due to their ability to produce alternative, viable solid forms when a more standard approach of salt and polymorph formation fails to deliver the desired objectives. Over the past few years, a number of papers have been published focusing on a broad range of subjects, from traditional crystal engineering to structure-property relationships of cocrystals. The present review, however, illustrates how the cocrystalline forms of APIs have improved their in vitro dissolution rate and in vivo bioavailability, often correlating well with their improved solubility as well.

Equilibrium solubility measurement of ionizable drugs – consensus recommendations for improving data quality

“…Interest in pharmaceutical cocrystals emerged rapidly in the last decade [30,[87][88][89][90][91][92][93][94][95][96]. Quite often cocrystals can be formed in the physical mixtures of the two components even without any action, merely due to moisture sorption by components themselves [97], or by a polymer excipient [96,98].…”

Solid self-nanoemulsifying drug delivery system (S-SNEDDS) for oral delivery of glimepiride: development and antidiabetic activity in albino rabbits

“…In these drugs, dissolution of the drug is the rate limiting step in the absorption process. To triumph over these obstacles, numbers of formulation approaches are reported including the use of surfactants (Allaboun et al, 2003;Balakrishnan et al, 2004;Chakraborty et al, 2009), lipids (Yeap et al, 2013), permeation enhancers (Burcin et al, 2010;Beg et al, 2011), formation of salt (Li et al, 2005;Serajuddin, 2007), co-crystallization (Shan & Zaworotko, 2008;Qiao et al, 2011;Chadha et al, 2012), solid dispersions (Serajuddin, 1999), inclusion complexes with cyclodextrins and modified cyclodextrins (Miyake et al, 2000;Veiga et al, 2000;Wang et al, 2000;Bannwart et al, 2001;Carrier et al, 2007;Gamsiz et al, 2010a,b;Gamsiz et al, 2011;Badr-Eldin et al, 2008;Kumar et al, 2013), nanosuspensions (Patravale et al, 2004), and colloidal vesicles like liposomes (Nazzal et al, 2002a;Manconi et al, 2013;Yang et al, 2013), and niosomes (Khazaeli et al, 2007;Bayindir & Yuksel, 2010;SezginBayindir et al, 2013;Jin et al, 2013) In modern years, self-nanoemulsifying drug delivery systems (SNEDDS) are the most popular and commercially feasible lipid-based formulation approach for improving oral bioavailability of poorly water soluble and lipophilic drugs (Pouton, 2006;Date, 2007;Shweta et al, 2011). SNEDDS are precisely defined as an isotropic multi-component drug delivery systems composed of a synthetic or natural oil, surfactant, and co-surfactant that have a unique ability of forming fine oil in water micro-or nano-emulsion upon mild agitation followed by dilutio...…”

In silico screening of dicarboxylic acids for cocrystallization with phenylpiperazine derivatives based on both cocrystallization propensity and solubility advantage

“…Indeed, there are numerous examples of the advantages of drug cocrystallization, including improvements in the pharmacodynamic characteristics of APIs [6, 7]. However, while its advantageous effects on solubility [8], dissolution rate, and the dose–response relationship [9] as well as the possibility of synergistic effects caused by the cooperative action of several active substances [10] are all good reasons for attempting API cocrystallization [11], other physicochemical characteristics of drugs can also be improved by cocrystallization [12, 13]. For instance, cocrystallization has been employed to lower hygroscopicity [14, 15], increase physical or chemical stability [16, 17], modulate [18] and maintain [19] color, improve mechanical properties [14], control morphological characteristics, reduce the diversity of active forms of the substance [20], and to address issues relating to the patenting [21] of new solid forms of drugs [22].…”