Please login first
Cocrystals of Modafinil-Nicotinic acid:A Novel Cocrystal for Enhanced Bioavailability
* 1 , 2 , 2 , 2
1  Department of Pharmaceutics, Faculty of Pharmacy, MS Ramaiah University of Applied Sciences
2  Department of Pharmaceutics, Bapuji Pharmacy College, Davangere, Karnataka, India

Published: 05 November 2020 by MDPI in The 2nd International Online Conference on Crystals session Crystal Engineering

In this work, we are the first to identify and report pharmaceutically effective cocrystals of poorly soluble drug Modafinil (MOD) using crystal engineering approach. A multi-component system of MOD with nicotinic acid (NIC) as coformer at 1:1 molar ratio was prepared to simultaneously improve solubility, dissolution and bioavailability by applying liquid assistant grinding technique. Nicotinic acid as a potential coformer for cocrystal preparation was predicted using a novel approach of Hansen Solubility Parameter (HSP) group contribution method. Various evaluation parameters pertaining to confirm cocrystal formation like Fourier Transformer Infrared spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), Powder X-Ray Diffraction (PXRD), and Field Emission Scanning Electron Microscopy (FESEM) were carried out. Further effect of precipitation inhibitors (HPMC) on in-vivo bioavailability enhancement was also studied. MOD-NIC cocrystals formation was confirmed by integrating results of instrumental techniques. Aqueous solubility and in-vivo pharmacokinetic study proved 5.96 and 1.88 times higher bioavailability respectively in case of prepared cocrystals compared to MOD alone whereas bioavailability further increased by 2.72 times when these cocrystals were administered in presence of precipitation inhibitor. Hence, solid state manipulation was successful for preparing modafinil cocrystals as a potential method for illustrating several properties. The concept of cocrystals coupled with precipitation inhibitors significantly enhanced the bioavailability of modafinil.

Keywords: Modafinil; Coformer; Cocrystals; Characterization; Bioavailability
Comments on this paper
Catherine Raptopoulou
This is an interesting work. I would like to ask the authors if they had tried to prepare single crystals of the MOD-NIC cocrystals for signle-crystal X-ray analysis.
Tanmoy Ghosh
No, our attempt was to prepare co-crystals of the API for enhancement of solubility and gastro-intestinal bioavailability. Single crystal preparation was not our target, but we tried to formulate few polymorphs of the same, but stability was an issue with polymorphs we tried.

Zoran Radić
Thank you for this interesting presentation. Are you planning on confirming your results in a different animal species? Would different route of administration affect bioavailability?
Tanmoy Ghosh
Since the oral route is the preferred route of administration, therefore we carried out an in-vivo study using the oral route. Other in-vivo models can also be tried to check the bioavailability enhancement, though we didn't still plan the same. For the parenteral route model, few more Physico-chemical evaluation of the co-crystals needs to be carried out. Thanks for the idea.. definitely we will look into that aspect in the future.

Changquan Calvin Sun
Modafinil-Nicotinic acid
This is another example that shows the potential benefits cocrystals can offer. I look forward to it publication as an research article.

Paola Paoli
Modafinil-Nicotinic acid cocrystals
Thank you for the interesting contribution which shows the usefulness of the “cocrystal” approach for the improvement of the biologically relevant properties of APIs. Just a comment on the XRPD patterns in figure 2: the pattern of the Modafinil-Nicotinic acid cocrystal sample appears very similar to the sum of the API and conformer XRPD patterns. As a consequence I would suggest that the authors also report and comment the results obtained with the others techniques to confirm the cocrystal formation.
Tanmoy Ghosh
Thanks for your observation, even we were a little doubtful at the start and so we carried out a PXRD study for the physical mixture of MOD-NIC and the difference we could observe. Further, we have carried out other studies like DSC, DTA to confirm the cocrystal formation.

Jesus Sanmartín-Matalobos
Why niacin as a coformer to obtain a cocrystal with improved bioavailability?
Thanks for a very easy to follow presentation. Please, could you tell me what reasons, in addition to its obvious safety at low doses and its solubility in water, have you taken into account in the selection of niacin as a coformator to obtain a cocrystal with better bioavailability?
Tanmoy Ghosh
It's not niacin, it's nicotinic acid selected on the basis of solubility parameter calculation. nicotinic acid is widely researched as a conformer for such type of works.

Jesus Sanmartín-Matalobos
Thanks for the answer. I have used the term niacin because it is the generic name for nicotinic acid (pyridine-3-carboxylic acid) and related derivatives.
Tanmoy Ghosh
Ya thanks for reminding me, sorry I guessed ur question wrongly. We used nicotinic acid as literature says its a water-soluble vitamin with a relatively simple organic molecular structure and also found in GRAS list of USFDA. Moreover we tried with total 9 coformers out of which 2 cocrystals we were able to characterise, others mainly being eutectics or physical mixture . One of these 2 is reported in this conference paper.

Jesus Sanmartín-Matalobos
Thanks for your answer.
Best wishes