A novel solubilization technique for poorly soluble drugs through the integration of nanocrystal and cocrystal technologies

Karashima, Masatoshi; Kimoto, Kouya; Yamamoto, Katsuhiko; Kojima, Takashi; Ikeda, Yukihiro

doi:10.1016/j.ejpb.2016.07.006

Cited by 59 publications

(57 citation statements)

References 49 publications

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“…Two systems of donepezil hydrochloride and donepezil solvate (DP-M) with two coformers (salicylic acid and p-aminobenzoic acid (PABA) were prepared based on a cogrinding method. FTIR, 13 C and 1 H NMR, PXRD, and DSC analysis confirmed the process-induced cocrystal salt and cocrystal formations from a solventfree method. Furthermore, this appears to be the first report of the formations of donepezil with paminobenzoic acid.…”

Section: Discussionmentioning

confidence: 62%

“…Cocrystallization can generate new crystal structures and may produce forms that provide properties beneficial for an oral dosage drug [8][9][10][11] . To date, most of the literature on cocrystals of APIs has focused on poorly soluble market drugs [12][13][14] . Industrial processing has primarily concentrated on producing neutral drugs that contain an amine, examples are fexofenadine and paroxetin.…”

Section: Introductionmentioning

confidence: 99%

“…(a)13 C NMR spectra of DH, DH-SA, and DH-PABA; (b) 1 H NMR spectra of DH, SA, and DH-SA; (c) 1 H NMR spectra of DH, PABA, DH-PABA, and DP-M-PABA.…”

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Characterization of donepezil prepared by cogrinding with salicylic acid and p-aminobenzoic acid

Somphon¹,

Makatan²

2019

ScienceAsia

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Two systems for the formation of cocrystals of donepezil were investigated using donepezil hydrochloride and donepezil solvate with salicylic acid and p-aminobenzoic acid. The donepezil solvate was prepared through an acidbase reaction between a hydrochloride salt and a base in methanol. Donepezil HCl (DH) and the solvate with salicylic acid and p-aminobenzoic acid (PABA) at 1:1 molar ratios were prepared using the cogrinding method. Cocrystals were characterized using attenuated total reflection-FTIR spectroscopy (ATR-FTIR), nuclear magnetic resonance spectroscopy (13 C and 1 H NMR), Powder X-ray diffraction, and differential scanning calorimetry. These results indicate that the cogrinding process could induce cocrystal formation in donepezil systems through a simple process that allows for rapid screening of cocrystals of donepezil.

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Section: Discussionmentioning

confidence: 62%

Section: Introductionmentioning

confidence: 99%

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Characterization of donepezil prepared by cogrinding with salicylic acid and p-aminobenzoic acid

Somphon¹,

Makatan²

2019

ScienceAsia

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“…If the polymer does not absorb on API surface, the steric hindrance effect does not work to prevent the aggregation. 46) Surface tensions of each polymer solutions were already reported for water-72 mN/m, HPC-44 mN/m, HPMC-48 mN/m, PVP-69 mN/m, and PVA-74 mN/m regardless of polymer concentration. 40) Given that HPC had low surface tension, it could be derived that it is the appropriate polymer for wet-beads milling.…”

Section: Dispersing Agent Screening Particle Size Distribution Of Frementioning

confidence: 73%

Development of Universal Formulation with Superior Re-dispersion Using Nanocrystal Approach with Simultaneous Identification of API Physicochemical Properties

Fujii

Watano

2019

CHEMICAL & PHARMACEUTICAL BULLETIN

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Universal nanocrystal formulation which can be applied to water-insoluble compounds was proposed and the criteria of its physicochemical properties as an active pharmaceutical ingredients (API) were investigated. Nanocrystal suspension was prepared by a wet-beads milling method. An acceptable Critical Quality Attributes (CQA) of nanocrystal suspension was defined by Z-average less than 500 nm and Polydispersity index (PDI) less than 0.3. Screening studies of dispersing and wetting agents were conducted using three model compounds in different pK a , melting points, etc., to find universal nanocrystal formulation. The effect of four structurally different polymer species (hydroxypropyl cellulose (HPC), hydoroxypropyl methylcellulose (HPMC), polyvinylpyrrolidone (PVP) and polyvinyl alcohol (PVA)) and their different grades or five different surfactants (docusate sodium (DOSS), sodium lauryl sulfate (SLS), cetyl trimethyl ammonium bromide (CTAB), polysolbate80 (PS80), and polyoxyethylene castor oil (CO-35)) were studied on the redispersion stability. It was found that the combination of 4% (w/v) HPC-SSL and 0.2% (w/v) DOSS was the most robust nanocrystal formulation owing to Z-average less than 200 nm and good re-dispersion stability without aggregates at pH 1.2 and pH 6.8. API physicochemical properties were also identified using ten water-insoluble compounds. Consequently, it was found that solubility (water, pH 1.2 and pH 6.8), molecular weight, hydrogen bonding acceptor and the ratio of log D 7.4 to C Log P were critical factors.

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“…About 40% of drugs and more than 70% of candidate drugs in current pharmaceutical development reportedly display poor aqueous solubility. The typical problems associated with poorly soluble drugs include low bioavailability and/or erratic absorption, reducing their therapeutic efficacy [1][2][3]. Therefore, increasing the dissolution rates of poorly watersoluble drugs is one of the most challenging issues for pharmaceutical scientists and engineers.…”

Section: Introductionmentioning

confidence: 99%

Fabrication of multicomponent amorphous bufadienolides nanosuspension with wet milling improves dissolution and stability

Zuo

et al. 2017

Artificial Cells, Nanomedicine, and Biotechnology

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Multicomponent formulations have attracted increasing attention because of their favourable patient compliance and greater therapeutic effect. The aim of this study was to develop a multicomponent nanosuspension formulation of bufadienolides, the antitumor components of a traditional Chinese medicine, toad venom, using a wet-milling technique to improve its dissolution behaviour. Croscarmellose sodium (CCS) and sodium lauryl sulfate (SLS) were chosen as the combined stabilizers of the nanosuspension. A Taguchi orthogonal array design was used for this study to optimize the formulation and process parameters. The optimized nanosuspension was characterized by its particle size distribution, zeta potential, morphology, crystallinity, molecular interactions, stability and dissolution. The results showed that the nanosuspension was a homogeneous amorphous system with average particle sizes of <100 nm and significantly improved dissolution behaviour. It was also physically stable for at least 2 months; steric and kinetic stabilization were its main stability mechanisms. These findings suggested that the use of wet milling to fabricate nanosuspensions is a promising method for achieving the fast and synchronized dissolution of multicomponent formulations, presumably increasing the bioavailability of poorly water-soluble drugs.

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A novel solubilization technique for poorly soluble drugs through the integration of nanocrystal and cocrystal technologies

Cited by 59 publications

References 49 publications

Characterization of donepezil prepared by cogrinding with salicylic acid and p-aminobenzoic acid

Characterization of donepezil prepared by cogrinding with salicylic acid and p-aminobenzoic acid

Development of Universal Formulation with Superior Re-dispersion Using Nanocrystal Approach with Simultaneous Identification of API Physicochemical Properties

Fabrication of multicomponent amorphous bufadienolides nanosuspension with wet milling improves dissolution and stability

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