Drug-drug co-crystals

The idea of developing multi-API co-crystals is interesting. This is reflected from the number of publications and patent applications for co-crystals in recent years. Drug-drug co-crystals fulfil the criteria for patent eligibility: novelty, utility, and non-obviousness for pharmaceutical development. However, no compilation of drug-drug co-crystals information’s is available in literature. There is immense potential to explore co-crystal design of established APIs among each other to enhance solubility and bioavailability of the product. Consequently, there is a strong need to devise ways to increase the likelihood of success in generating drug–drug co-crystals. In this context, the limited available reports in literature are described here. While co-administering a combination of theophylline and phenobarbital, it was discovered that a co-crystal of 2:1 stoichiometry existed between the two compounds [2]. The example of a trimorphic co-crystal involving APIs i.e. ethenzamide and gentisic acid, may find relevance in the context of combination drugs [3]. The meloxicam-aspirin co-crystal decreased the time required to reach the human therapeutic concentration compared with the parent drug, meloxicam [4]. Higher degree of solubility of acetylsalicylic acid: (L)-theanine [(L)-5-N-ethyl-glutamine] co-crystal system enables aspirin formulations for intravenous administration [5]. The 1:1 acetaminophen/theophylline (AT) co-crystal had a faster dissolution rate than AT physical mixtures [6]. Pharmaceutical composition comprising therapeutically effective amount of lamivudine: zidovudine co-crystals use for manufacture of medicament for treatment of HIV infections of humans was reported [7]. A single step co-deposition of albuterol sulphate: ipratropium bromide co-crystal aerosols was reported [8]. Two 1:1 drug-drug co-crystals [isoniazid: 4-aminosalicylic acid; pyrazinamide: 4-aminosalicylic acid] may be exploited for the treatment of tuberculosis [9]. Celecoxib: venlafax