Influence of Solvent Composition on the Miscibility and Physical Stability of Naproxen/PVP K 25 Solid Dispersions Prepared by Cosolvent Spray-Drying

This work describes a novel screening strategy that implements small-scale spray-drying in early development of binary amorphous solid dispersions (ASDs). The proposed methodology consists of a three-stage decision protocol in which small batches (20–100 mg) of spray-dried solid dispersions (SDSDs) are evaluated in terms of drug–polymer miscibility, physical stability and dissolution performance in bio-predictive conditions. The objectives are to select the adequate carrier and drug-loading (DL) for the manufacturing of robust SDSD; and the appropriate stabilizer dissolved in the liquid vehicle of SDSD suspensions, which constitutes the common dosage form used during non-clinical studies. This methodology was verified with CDP146, a poorly water soluble (<2 µg/mL) API combined with four enteric polymers and four stabilizers. CDP146/HPMCAS-LF 40:60 (w/w) and 10% (w/v) PVPVA were identified as the lead SDSD and the best performing stabilizer, respectively. Lead SDSD suspensions (1–50 mg/mL) were found to preserve complete amorphous state during 8 h and maintain supersaturation in simulated rat intestinal fluids during the absorption window. Therefore, the implementation of spray-drying as a small-scale screening approach allowed maximizing screening effectiveness with respect to very limited API amounts (735 mg) and time resources (9 days), while removing transfer steps between screening and manufacturing phases.

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Effect of Storage Humidity on Physical Stability of Spray-Dried Naproxen Amorphous Solid Dispersions with Polyvinylpyrrolidone: Two Fluid Nozzle vs. Three Fluid Nozzle

Pharmaceutics ◽

10.3390/pharmaceutics13071074 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1074

Author(s):

Sonal V. Bhujbal ◽

Yongchao Su ◽

Vaibhav Pathak ◽

Dmitry Y. Zemlyanov ◽

Alex-Anthony Cavallaro ◽

...

Keyword(s):

Spray Drying ◽

Single Channel ◽

Solid Dispersions ◽

Physical Stability ◽

Volume Ratio ◽

Amorphous Solid ◽

Drug Dissolution ◽

Amorphous Solid Dispersions ◽

Two Fluid ◽

Spray Dried

In a spray drying operation, a two-fluid nozzle (2FN) with a single channel is commonly used for atomizing the feed solution. However, the less commonly used three-fluid nozzle (3FN) has two separate channels, which allow spray drying of materials in two incompatible solution systems. Although amorphous solid dispersions (ASDs) prepared using a 3FN have been reported to deliver comparable drug dissolution performance relative to those prepared using a 2FN, few studies have systematically examined the effect of 3FN on the physical stability. Therefore, the goal of this work is to systematically study the physical stability of ASDs that are spray-dried using a 3FN compared to those prepared using the traditional 2FN. For the 2FN, a single solution of naproxen and polyvinylpyrrolidone (PVP) was prepared in a mixture of acetone and water at a 1:1 volume ratio because 2FN allows for only one solution inlet. For the 3FN, naproxen and PVP were dissolved individually in acetone and water, respectively, because 3FN allows simultaneous entry of two solutions. Upon storage of the formulated ASDs at different humidity levels (25%, 55% and 75% RH), naproxen crystallized more quickly from the 3FN ASDs as compared with the 2FN ASDs. 3FN ASDs crystallized after 5 days of storage at all conditions, whereas 2FN ASDs did not crystallize even at 55% RH for two months. This relatively higher crystallization tendency of 3FN ASDs was attributed to the inhomogeneity of drug and polymers as identified by the solid-state Nuclear Magnetic Resonance findings, specifically due to poor mixing of water- and acetone-based solutions at the 3FN nozzle. When only acetone was used as a solvent to prepare drug-polymer solutions for 3FN, the formulated ASD was found to be stable for >3 months of storage (at 75% RH), which suggests that instability of the 3FN ASD was due to the insufficient mixing of water and acetone solutions. This study provides insights into the effects of solvent and nozzle choices on the physical stability of spray-dried ASDs.

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Solid Dispersions with Anionic EUDRAGIT&[reg] Polymers Using Spray Drying Technique to Increase the Solubility of Poorly Soluble Drugs

10.26226/morressier.57d6b2bdd462b8028d88d414 ◽

2016 ◽

Author(s):

Jitendra Amrutkar

Keyword(s):

Spray Drying ◽

Solid Dispersions ◽

Poorly Soluble Drugs ◽

Poorly Soluble

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Influence of β-Cyclodextrin and Hydroxypropyl-β-Cyclodextrin on Enhancement of Solubility and Dissolution of Isradipine

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2017.10.3.8 ◽

2017 ◽

Vol 10 (3) ◽

pp. 3752-3757

Author(s):

Narendar D ◽

Ettireddy S

Keyword(s):

Inclusion Complex ◽

Dissolution Rate ◽

Solid Dispersions ◽

Physical Stability ◽

Molecular Complexes ◽

In Vitro Dissolution ◽

Molar Ratio ◽

Phase Solubility ◽

Cyclodextrin Complexation

The content of this investigation was to study the influence of β-cyclodextrin and hydroxy propyl-β-cyclodextrin complexation on enhancement of solubility and dissolution rate of isradipine. Based on preliminary phase solubility studies, solid complexes prepared by freeze drying method in 1:1 molar ratio were selected and characterized by DSC for confirmation of complex formation. Prepared solid dispersions were evaluated for drug content, solubility and in vitro dissolution. The physical stability of optimized formulation was studied at refrigerated and room temperature for 2 months. Solid state characterization of optimized complex performed by DSC and XRD studies. Dissolution rate of isradipine was increased compared with pure drug and more with HP-β-CD inclusion complex than β-CD. DSC and XRD analyzes that drug was in amorphous form, when the drug was incorporated as isradipine β-CD and HP-β-CD inclusion complex. Stability studies resulted in low or no variations in the percentage of complexation efficiency suggesting good stability of molecular complexes. The results conclusively demonstrated that the enhancement of solubility and dissolution rate of isradipine by drug-cyclodextrin complexation was achieved.

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Enhanced Oral Bioavailability of Resveratrol by Using Neutralized Eudragit E Solid Dispersion Prepared via Spray Drying

Antioxidants ◽

10.3390/antiox10010090 ◽

2021 ◽

Vol 10 (1) ◽

pp. 90

Author(s):

Eun-Sol Ha ◽

Du Hyung Choi ◽

In-hwan Baek ◽

Heejun Park ◽

Min-Soo Kim

Keyword(s):

Spray Drying ◽

Solid Dispersion ◽

Oral Bioavailability ◽

Solid Dispersions ◽

Amorphous Solid ◽

Pharmaceutical Products ◽

In Vitro Dissolution ◽

Dependent Manner ◽

Amorphous Solid Dispersions ◽

Eudragit E

In this study, we designed amorphous solid dispersions based on Eudragit E/HCl (neutralized Eudragit E using hydrochloric acid) to maximize the dissolution of trans-resveratrol. Solid-state characterization of amorphous solid dispersions of trans-resveratrol was performed using powder X-ray diffraction, scanning electron microscopy, and particle size measurements. In addition, an in vitro dissolution study and an in vivo pharmacokinetic study in rats were carried out. Among the tested polymers, Eudragit E/HCl was the most effective solid dispersion for the solubilization of trans-resveratrol. Eudragit E/HCl significantly inhibited the precipitation of trans-resveratrol in a pH 1.2 dissolution medium in a dose-dependent manner. The amorphous Eudragit E/HCl solid dispersion at a trans-resveratrol/polymer ratio of 10/90 exhibited a high degree of supersaturation without trans-resveratrol precipitation for at least 48 h by the formation of Eudragit E/HCl micelles. In rats, the absolute oral bioavailability (F%) of trans-resveratrol from Eudragit E/HCl solid dispersion (10/90) was estimated to be 40%. Therefore, trans-resveratrol-loaded Eudragit E/HCl solid dispersions prepared by spray drying offer a promising formulation strategy with high oral bioavailability for developing high-quality health supplements, nutraceutical, and pharmaceutical products.

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