Pharmaceutical Cocrystals: Regulatory and Strategic Aspects, Design and Development

Gadade, Dipak D.; Pekamwar, Sanjay S.

doi:10.15171/apb.2016.062

Cited by 122 publications

(92 citation statements)

References 118 publications

(73 reference statements)

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“…Multiple approaches have been adopted to improve the solubility of poorly water soluble APIs including micronization [2] , complexation with cyclodextrins [3] , cosolvency [4,5] , solid dispersions [6] , salt forms [7] , nanoparticles [8] and surfactants [9] , etc. Cocrystals are a class of multicomponent molecular crystals demonstrated to enhance the solubility, bioavailability and/or stability of API, which has been proposed as a unique crystal engineering approach to alter the physicochemical properties of compounds [10][11][12] . According to recently published guidance by the United States Food and Drug Administration (USFDA) cocrystals are defined as, 'crystalline materials composed of two or more molecules within the same crystal lattice [13] .…”

Section: Research Papermentioning

confidence: 99%

Solubility Enhancement of Lornoxicam by Crystal Engineering

Gadade¹,

Kulkarni²,

Rathi³

et al. 2017

Journal of Pharmaceutical Sciences

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Gadade, et al.: Crystal Engineering of LornoxicamAn attempt was made to improve the solubility and physicochemical properties of the poorly soluble lornoxicam by crystal engineering with different coformers. Nineteen different coformers were screened during this study. Cocrystals were prepared by neat grinding method. The prepared cocrystals were evaluated for solubility, powder characteristics, assay and in vitro dissolution study. The solid state property was characterized by differential scanning calorimetry, Fourier transform infrared spectroscopy, powder X-ray diffraction analysis and Raman spectroscopy. Maximum solubility and dissolution rate were observed with cocrystal prepared using saccharin sodium. Cocrystallization leads to increased solubility and improved in vitro dissolution of lornoxicam.

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Section: Research Papermentioning

confidence: 99%

Solubility Enhancement of Lornoxicam by Crystal Engineering

Gadade¹,

Kulkarni²,

Rathi³

et al. 2017

Journal of Pharmaceutical Sciences

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“…Many challenges have been described in the literature during translational development of pharmaceutical cocrystals such as: safety of the coformers, polymorphic form, solvates, hydrates, salts [33], traces of co-amorphous domains, unpredictable performance during dissolution and difficulties in establishing in vitro-in vivo correlation [34]. Most of these issues are highly dependent on the type of manufacturing process utilised to produce the cocrystal [35].…”

Section: Discussionmentioning

confidence: 99%

Optimising the in vitro and in vivo performance of oral cocrystal formulations via spray coating

Serrano

Walsh

O’Connell

et al. 2018

European Journal of Pharmaceutics and Biopharmaceutics

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Engineering of pharmaceutical cocrystals is an advantageous alternative to salt formation for improving the aqueous solubility of hydrophobic drugs. Although, spray drying is a well-established scale-up technique in the production of cocrystals, several issues can arise such as sublimation or stickiness due to low glass transition temperatures of some organic molecules, making the process very challenging. Even though, fluidised bed spray coating has been successfully employed in the production of amorphous drug-coated particles, to the best of our knowledge, it has never been employed in the production of cocrystals. The feasibility of this technique was proven using three model cocrystals: sulfadimidine (SDM)/4-aminosalicylic acid (4ASA), sulfadimidine/nicotinic acid (NA) and ibuprofen (IBU)/ nicotinamide (NAM). Design of experiments were performed to understand the critical formulation and process parameters that determine the formation of either cocrystal or coamorphous systems for SDM/4ASA. The amount and type of binder played a key role in the overall solid state and in vitro performance characteristics of the cocrystals. The optimal balance between high loading efficiencies and high degree of crystallinity was achieved only when a binder: cocrystal weight ratio of 5:95 or 10:90 was used. The cocrystal coated beads showed an improved in vitro-in vivo performance characterised by: (i) no tendency to aggregate in aqueous media compared to spray dried formulations, (ii) enhanced in vitro activity (1.8-fold greater) against S. aureus, (iii) larger oral absorption and bioavailability (2.2-fold higher C), (iv) greater flow properties and (v) improved chemical stability than cocrystals produced by other methods derived from the morphology and solid nature of the starter cores.

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“…Over the last 15 years, the production of pharmaceutical co-crystals has gained an increased attention to overcome the problems associated with the poorly-water soluble drugs, and more recently co-amorphous systems have also been produced [39,40]. By definition, co-crystals (also called multi-component crystals) are crystalline materials composed by two or more different components in a well-defined stoichiometric ratio [41]. These components are usually an active pharmaceutical ingredients (API) and a co-crystal former, which can be an excipient or another drug [42].…”

Section: Co-crystalsmentioning

confidence: 99%

Production of pure drug nanocrystals and nano co-crystals by confinement methods

Fontana

Figueiredo

Zhang

et al. 2018

Advanced Drug Delivery Reviews

134

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The use of drug nanocrystals in the drug formulation is increasing due to the large number of poorly water-soluble drug compounds synthetized and due to the advantages brought by the nanonization process. The downsizing processes are done using a top-down approach (milling and homogenization currently employed at the industrial level), while the crystallization process is performed by bottom-up techniques (e.g., antisolvent precipitation, use of supercritical fluids or spray and freeze drying). In addition, the production of nanocrystals in confined environment can be achieved within microfluidics channels. This review analyzes the processes for the preparation of nanocrystals and co-crystals, divided by top-down and bottom-up approaches, together with their combinations. The combination of both strategies merges the favorable features of each process and avoids the disadvantages of single processes. Overall, the applicability of drug nanocrystals is highlighted by the widespread research on the production processes at the engineering, pharmaceutical, and nanotechnology level.

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Pharmaceutical Cocrystals: Regulatory and Strategic Aspects, Design and Development

Cited by 122 publications

References 118 publications

Solubility Enhancement of Lornoxicam by Crystal Engineering

Solubility Enhancement of Lornoxicam by Crystal Engineering

Optimising the in vitro and in vivo performance of oral cocrystal formulations via spray coating

Production of pure drug nanocrystals and nano co-crystals by confinement methods

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