An investigation into solubility and dissolution improvement of alectinib hydrochloride as a third-generation amorphous solid dispersion

Saha, Sumit Kumar; Joshi, Amita; Singh, Rajiv; Jana, Suvamay; Dubey, Kiran

doi:10.1016/j.jddst.2023.104259

Cited by 16 publications

(7 citation statements)

References 43 publications

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“…It has exhibited great potential in the improvement of solubility, dissolution, and bioavailability of drugs with various physicochemical properties as well as enhancing drug wettability. For this reason, Soluplus ® was incorporated in all polymeric combinations (Saha et al, 2023). ASDs were prepared by means of microfluidic-on-a-chip equipment with an AS:S ratio of 50:50 (% V/V), following the formulation compositions displayed in Table 2.…”

Section: Tailoring Polymer Composition Based On the Intrinsic Dissolu...mentioning

confidence: 99%

“…During the last decades, both academic and industrial research has been demonstrating the potential of amorphous solid dispersions (ASDs) in overcoming the challenge posed by poor water solubility of drugs. The amorphous form exhibits a disarrangement in the crystal lattice of its crystalline counterpart, generating a higher state of free energy, allowing the drug to achieve greater apparent solubility and faster dissolution (Saha et al, 2023). However, the amorphous form is metastable and tends to convert to a more stable crystalline form.…”

Section: Introductionmentioning

confidence: 99%

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Microfluidic-on-a-chip for designing celecoxib-based amorphous solid dispersions: when the process shapes the product

Figueiredo,

Mendes,

Pais

et al. 2024

Preprint

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The fundamental idea underlying the use of amorphous solid dispersions (ASDs) is to make the most of the solubility advantage of the amorphous form of a drug. However, the drug stability becomes compromised due to the higher free energy and disorder of molecular packing in the amorphous phase, leading to crystallization. To overcome the stability concern, polymers are used as a matrix to form a stable homogeneous amorphous system. The present work aims to design ASD-based formulations under the quality umbrella by design principles for improving oral drug bioavailability, using celecoxib (CXB) as a model drug. ASDs were prepared from selected polymers and tested both individually and in combinations, using various manufacturing techniques: high-shear homogenization, high-pressure homogenization, microfluidic-on-a-chip, and spray-drying. The resulting dispersions were further optimized, resorting to a 32 full-factorial design, considering the API:Polymers ratio and the total solid content as variables. The formulated products were evaluated regarding analytical centrifugation and the influence of the different polymers on the intrinsic dissolution rate of the CXBASDs. Microfluidic-on-a-chip led to amorphous status of the formulation. The in vitro evaluation demonstrated a remarkable 26-fold enhancement in the intrinsic dissolution rate, and the translation of this formulation into tablets as the final dosage form is consistent with the observed performance enhancement. These findings are supported by ex vivo assays, which exhibited a two-fold increase in permeability compared to pure CXB. This study tackles the bioavailability hurdles encountered with diverse active compounds, offering insights into the development of more effective drug delivery platforms.

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Section: Tailoring Polymer Composition Based On the Intrinsic Dissolu...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Microfluidic-on-a-chip for designing celecoxib-based amorphous solid dispersions: when the process shapes the product

Figueiredo,

Mendes,

Pais

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…In a study, Lauretta et al have reported that amorphous ternary solid dispersion of poorly soluble gliclazid (used in the treatment of patients with type 2 diabetes) with crosslinked PVP and SLS by comilling technique exhibited a higher dissolution rate (90% in 2 h) compared to the commercial product Diabrezide [30]. Additionally, Saha Sumit et al have stated that third-generation solid dispersion of alectinib hydrochloride by solvent evaporation technique resulted in increased drug solubility and dissolution using soluplus and different surfactants [31].…”

Section: Multimedia Dissolution Of the Final Formulationmentioning

confidence: 99%

Design, Optimization, and Characterization of a Novel Amorphous Solid Dispersion Formulation for Enhancement of Solubility and Dissolution of Ticagrelor

et al. 2023

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Objective: The study aims to enhance the solubility and dissolution of ticagrelor by formulating an amorphous solid dispersion using the hot melt extrusion technique. Methods: Solubility of ticagrelor is very limited in water and buffers of pH 1.2 to 6.8, which is one of the prime reasons for its low oral bioavailability. Amorphous solid dispersions were prepared using the Hot Melt Extrusion technique using different polymers, plasticizers, and surfactants. The formulation is optimized based on the level of polymer in the formulation. The final formulation of Ticagrelor Amorphous Solid Dispersion is made with a drug-polymer ratio of 1:3, keeping the plasticizer level at 10% of the polymer along with a surfactant Sodium Lauryl Sulfate. Results: The formulation showed an increase in solubility of 193.95-times in water, 50.71-times in 0.1 N HCl, 332.74-times in pH 4.5 acetate buffer, and 85.20-times in pH 6.8 phosphate buffer as compared to the pure drug. The drug release of the final formulation was found to be 70.0±4.4%, 55.4±1.1%, 35.5±2.1%, and 30.0±0.8% at 90 min, while the reference product showed a release of 9.4±1.1%, 20.7±0.5%, 8.4±0.3%, and 7.8±0.2% at 90 min in water, 0.1 N HCl, pH 4.5 acetate buffer and pH 6.8 Phosphate Buffer respectively. The drug release of the final formulation was found to be 99.1±3.8% at 60 min in 0.2% w/v Polysorbate-80 in water. Conclusion: In the present study, the amorphous solid dispersion of the poorly-soluble drug ticagrelor was successfully prepared. The polymer, Plasdone S630, is considered the most suitable with ticagrelor for formulating amorphous solid dispersion using Hot Melt Extrusion technology to increase the solubility and dissolution of the drug.

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“…To improve the solubility of hydrophobic drugs, various approaches utilizing different auxiliary agents have been reported [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. Among others, cyclodextrins open wide prospects not only of improving the solubility and regulation of drug release but also minimizing gastrointestinal and ocular irritation, and reducing or eliminating unpleasant taste and smell.…”

Section: Introductionmentioning

confidence: 99%

Controlling the Solubility, Release Rate and Permeation of Riluzole with Cyclodextrins

Volkova,

Simonova,

Perlovich

2024

Pharmaceutics

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Riluzole (RLZ), a sodium channel-blocking benzothiazole anticonvulsant BCS class II drug, is very slightly soluble in aqueous medium. To improve aqueous solubility and modulate dissolution rate and membrane permeability, complex formation of RLZ with two cyclodextrin, α-cyclodextrin (α-CD) and sulfobutylether-β-cyclodextrin (SBE-β-CD), was studied. The stability constants demonstrated a greater affinity of SBE-β-CD towards RLZ compared to α-CD. A solubility growth of 1.7-fold and 3.7-fold with α-CD and SBE-β-CD, respectively, was detected in the solutions of 1% cyclodextrins and accompanied by the permeability reduction. For 1% CD solutions, several biopolymers (1% w/v) were tested for the membrane permeability under static conditions. The synergistic positive effect of α-CD and polymer on the solubility accompanied by unchanged permeability was revealed in RLZ/α-CD/PG, RLZ/α-CD/PEG400, and RLZ/α-CD/PEG1000 systems. Solid RLZ/CD complexes were prepared. Dynamic dissolution/permeation experiments for the solid samples disclosed the characteristic features of the release processes and permeation rate through different artificial membranes. The maximal permeation rate was determined across the hydrophilic semi-permeable cellulose membrane followed by the lipophilic PermeaPad barrier (model of intestinal and buccal absorption) and polydimethylsiloxane-polycarbonate membrane (simulating transdermal delivery way). Different mode of the permeation between the membranes was estimated and discussed.

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An investigation into solubility and dissolution improvement of alectinib hydrochloride as a third-generation amorphous solid dispersion

Cited by 16 publications

References 43 publications

Microfluidic-on-a-chip for designing celecoxib-based amorphous solid dispersions: when the process shapes the product

Microfluidic-on-a-chip for designing celecoxib-based amorphous solid dispersions: when the process shapes the product

Design, Optimization, and Characterization of a Novel Amorphous Solid Dispersion Formulation for Enhancement of Solubility and Dissolution of Ticagrelor

Controlling the Solubility, Release Rate and Permeation of Riluzole with Cyclodextrins

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