Development and Characterization of Dapsone Cocrystal Prepared by Scalable Production Methods

Abstract

In this study, the formation of caffeine/dapsone (CAF/DAP) cocrystals by scalable production methods, such as liquid-assisted grinding (LAG) and spray drying, was investigated in the context of the potential use of processed cocrystal powder for pulmonary delivery. A CAF/DAP cocrystal (1:1 M ratio) was successfully prepared by slow evaporation from both acetone and ethyl acetate. Acetone, ethyl acetate, and ethanol were all successfully used to prepare cocrystals by LAG and spray drying. The powders obtained were characterized by X-ray diffractometry (XRD), differential scanning calorimetry (DSC), thermogravimetry (TGA), and Fourier transform infrared spectroscopy (FTIR). Laser diffraction analysis indicated a median particle size (D) for spray-dried powders prepared from acetone, ethanol, and ethyl acetate of 5.4 ± 0.7, 5.2 ± 0.1, and 5.1 ± 0.0 μm respectively, which are appropriate sizes for pulmonary delivery by means of a dry powder inhaler. The solubility of the CAF/DAP cocrystal in phosphate buffer pH 7.4, prepared by spray drying using acetone, was 506.5 ± 31.5 μg/mL, while pure crystalline DAP had a measured solubility of 217.1 ± 7.8 μg/mL. In vitro cytotoxicity studies using Calu-3 cells indicated that the cocrystals were not toxic at concentrations of 0.1 and of 1 mM of DAP, while an in vitro permeability study suggested caffeine may contribute to the permeation of DAP by hindering the efflux effect. The results obtained indicate that the CAF/DAP cocrystal, particularly when prepared by the spray drying method, represents a possible suitable approach for inhalation formulations with applications in pulmonary pathologies.

Exploring Novel Cocrystalline Forms of Oxyresveratrol to Enhance Aqueous Solubility and Permeability across a Cell Monolayer

“…The cocrystals were to be non-toxic at concentrations up to 1 mM in in vitro cytotoxicity studies using Calu-3 cells and had better drug permeability than the drug alone by changing the efflux effect. 25) On the other hand, using the permeation apparatus with cellulose membrane, the enhanced dissolution and permeation properties of the cocrystals tested in the form of a powdered drug substance with and without polymers, 26) polymorphic cocrystals conducted in pH 1.2 and 7.4 solutions, 27,28) cocrystals with various coformers at a 1 : 1 ratio in phosphate buffer 29) and biologically active cocrystals stabilized via a certain lattice energy 30) have been revealed.…”

“…The slurry technique is highly efficient for cocrystal screening with the advantage over other traditional methods that cocrystal formation is not limited to noncongruent solubility of cocrystal components and has a flexible range in terms of physical stability of the phase diagram and solvent selection approaches based on thermodynamically driven solution-mediated phase transformation. [20][21][22][23][24] Compared to cocrystal physicochemical characterizations, permeation studies of cocrystal have been limited even though membrane permeability is one of the most important characteristics determining drug performance during absorption or bioavailability. The cocrystals were to be non-toxic at concentrations up to 1 mM in in vitro cytotoxicity studies using Calu-3 cells and had better drug permeability than the drug alone by changing the efflux effect.…”

Investigation of solid–liquid phase diagrams of the sulfamethazine–salicylic acid co-crystal

“…[36][37][38] There is also a limited amount of work performed so far on various aspects of their manufacturing. [39][40][41] For design and operation of a crystallization process for the manufacture of co-crystals, a complete and detailed phase diagram is crucial as it reveals the stability regions for the different crystalline phases. Based on a proper phase diagram identifying the region where the co-crystal is the stable solid phase, the conditions for manufacturing can be determined.…”

An Undergraduate Experiment Using Cyclodextrin – Assisted Sensitive Fluorescence Detection and Quantitation of Dapsone Drug in Wastewater Samples

“…Dapsone, also known as diaminodiphenyl sulfone (DDS), is an antibiotic drug commonly used for treatment of various skin disorders like leprosy, dermatitis and herpetiformis [1,2,3]. It has been studied extensively for pharmaceutical research such as bioavailability [4], biotransformation [5], and formulations, [6]. It has been detected in plasma, urine and saliva [7,8] using different analytical methods such as liquid chromatography with, UV-Visible [8], fluorescence [9] and mass spectrometry [10], as well as electrochemical detection [8].…”

“…The cyclodextrins (CDs) are cyclic oligosaccharides composed of multiple subunits of glucose in an (1,2,3,4) configuration. They are classified by the number of subunits (α = 6, β = 7, γ = 8) and by the type and degree of substitution.…”