Stability and Solubility of Celecoxib-PVP Amorphous Dispersions: A Molecular Perspective

Gupta, Piyush; Kakumanu, Vasu Kumar; Bansal, Arvind K.

doi:10.1023/b:pham.0000045226.42859.b8

Cited by 196 publications

(160 citation statements)

References 22 publications

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“…It is reported in the literature that the solubility and dissolution rate enhancement of a drug in amorphous state is caused by the formation of disordered structure of molecules which acquire higher free energy as compared to the molecules in ordered crystalline structure (25). The solubility of conventional prednisone and co-ground 1:7 prednisone-Neusilin complex were evaluated as a function of time in Fig.…”

Section: Solubility Measurementsmentioning

confidence: 99%

Development of a Mini-Tablet of Co-Grinded Prednisone–Neusilin Complex for Pediatric Use

et al. 2013

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Abstract. The purpose of this study is to enhance the dissolution rate of prednisone by co-grinding with Neusilin to form a complex that can be incorporated into a mini-tablet formulation for pediatrics. Prednisone-Neusilin complex was co-grinded at various ratios (1:1, 1:3, 1:5, and 1:7). The physicochemical properties of the complex were characterized by various analytical techniques including: differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), scanning electron microscope (SEM), particle size, surface area, solubility, and dissolution rate. The co-grinded prednisone-Neusilin complex (1:7) was blended with other excipients and was formulated into a 2-mm diameter mini-tablet. The minitablets were further evaluated for thickness, weight, content uniformity, and dissolution rate. To improve taste masking and stability, mini-tablets were coated by dip coating with Eudragit® EPO solution. DSC and XRPD results showed that prednisone was transformed from crystalline state into amorphous state after co-grinding with Neusilin. Particle size, surface area, and SEM results confirmed that prednisone was adsorbed to Neusilin's surface. Co-grinded prednisone-Neusilin complex (1:7) had a solubility of 0.24 mg/ mL and 90% dissolved within 20 min as compared to crystalline prednisone which had a solubility of 0.117 mg/mL and 30% dissolved within 20 min. The mini-tablets containing co-grinded prednisoneNeusilin complex (1:7) exhibited acceptable physicochemical and mechanical properties including dissolution rate enhancement. These mini-tablets were successfully dip coated in Eudragit® EPO solution to mask the taste of the drug during swallowing. This work illustrates the potential use of co-grinded prednisone-Neusilin to enhance solubility and dissolution rate as well as incorporation into a mini-tablet formulation for pediatric use.

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Section: Solubility Measurementsmentioning

confidence: 99%

Development of a Mini-Tablet of Co-Grinded Prednisone–Neusilin Complex for Pediatric Use

et al. 2013

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“…In order to circumvent crystallization and subsequent loss of the dissolution advantage, the amorphous drug can be dispersed in an amorphous polymer; a formulation strategy commonly referred to as an amorphous solid dispersion (6,7). Besides stabilizing the drug against crystallization in the solid state, the polymer can also further improve the dissolution profile through inhibition of the crystallization from the supersaturated solution generated upon dissolution (8,9).…”

Section: Introductionmentioning

confidence: 99%

Influence of Copolymer Composition on In Vitro and In Vivo Performance of Celecoxib-PVP/VA Amorphous Solid Dispersions

Knopp

Nguyen

et al. 2016

AAPS J

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Abstract. Previous studies suggested that an amorphous solid dispersion with a copolymer consisting of both hydrophobic and hydrophilic monomers could improve the dissolution profile of a poorly watersoluble drug compared to the crystalline form. Therefore, this study investigated the influence of the copolymer composition of polyvinylpyrrolidone/vinyl acetate (PVP/VA) on the non-sink in vitro dissolution behavior and in vivo performance of celecoxib (CCX) amorphous solid dispersions. The study showed that the hydrophilic monomer vinylpyrrolidone (VP) was responsible for the generation of CCX supersaturation whereas the hydrophobic monomer vinyl acetate (VA) was responsible for the stabilization of the supersaturated solution. For CCX, there was an optimal copolymer composition around 50-60% VP content where further replacement of VP monomers with VA monomers did not have any biopharmaceutical advantages. A linear relationship was found between the in vitro AUC 0-4h and in vivo AUC 0-24h for the CCX:PVP/VA systems, indicating that the non-sink in vitro dissolution method applied in this study was useful in predicting the in vivo performance. These results indicated that when formulating a poorly water-soluble drug as an amorphous solid dispersion using a copolymer, the copolymer composition has a significant influence on the dissolution profile and in vivo performance. Thus, the dissolution profile of a drug can theoretically be tailored by changing the monomer ratio of a copolymer with respect to the required in vivo plasma-concentration profile. As this ratio is likely to be drug dependent, determining the optimal ratio between the hydrophilic (dissolution enhancing) and hydrophobic (crystallization inhibiting) monomers for a given drug is imperative.

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“…Formulation approaches used to improve the oral bioavailability of poorly soluble compounds include inclusion complexation, nanoparticles, pro-drugs, cosolvents, micelles/emulsions, salts, co-crystals, and amorphous solids. Of these approaches, amorphous solids have recently drawn a high level of interest (1,2,12), and investigations on utilizing amorphous solids to improve oral bioavailability of poorly soluble drugs have been reported (1,2,(12)(13)(14)(15)(16)(17)(18). Unlike crystalline material, an amorphous solid is characterized as having a molecular arrangement that lacks long range order.…”

Section: Introductionmentioning

confidence: 99%

“…The current strategy to stabilize an amorphous solid is to create a solid dispersion amorphous drug polymer system (ASD). Various polymeric matrices have been reported to stabilize amorphous solids in solid dispersion drug polymer systems such as povidone, crospovidone, poloxamer, hydroxypropyl methylcellulose acetate succinate (HPMCAS), hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose, and hydroxypropyl-betacyclodextrin, polymethacrylates (1,2,9,(12)(13)(14)(15)(16)(17)(18)(19).…”

Section: Introductionmentioning

confidence: 99%

In Vitro and In Vivo Evaluation of Amorphous Solid Dispersions Generated by Different Bench-Scale Processes, Using Griseofulvin as a Model Compound

Chiang¹,

Cui²,

Ran³

et al. 2013

AAPS J

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Abstract. Drug polymer-based amorphous solid dispersions (ASD) are widely used in the pharmaceutical industry to improve bioavailability for poorly water-soluble compounds. Spray-drying is the most common process involved in the manufacturing of ASD material. However, spray-drying involves a high investment of material quantity and time. Lower investment manufacturing processes such as fast evaporation and freeze-drying (lyophilization) have been developed to manufacture ASD at the bench level. The general belief is that the overall performance of ASD material is thermodynamically driven and should be independent of the manufacturing process. However, no formal comparison has been made to assess the in vivo performance of material generated by different processes. This study compares the in vitro and in vivo properties of ASD material generated by fast evaporation, lyophilization, and spray-drying methods using griseofulvin as a model compound and hydroxypropyl methylcellulose acetate succinate as the polymer matrix. Our data suggest that despite minor differences in the formulation release properties and stability of the ASD materials, the overall exposure is comparable between the three manufacturing processes under the conditions examined. These results suggest that fast evaporation and lyophilization may be suitable to generate ASD material for oral evaluation. However, caution should be exercised since the general applicability of the present findings will need to be further evaluated.

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Stability and Solubility of Celecoxib-PVP Amorphous Dispersions: A Molecular Perspective

Cited by 196 publications

References 22 publications

Development of a Mini-Tablet of Co-Grinded Prednisone–Neusilin Complex for Pediatric Use

Development of a Mini-Tablet of Co-Grinded Prednisone–Neusilin Complex for Pediatric Use

Influence of Copolymer Composition on In Vitro and In Vivo Performance of Celecoxib-PVP/VA Amorphous Solid Dispersions

In Vitro and In Vivo Evaluation of Amorphous Solid Dispersions Generated by Different Bench-Scale Processes, Using Griseofulvin as a Model Compound

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