scholarly journals A Novel Protocol Using Small-Scale Spray-Drying for the Efficient Screening of Solid Dispersions in Early Drug Development and Formulation, as a Straight Pathway from Screening to Manufacturing Stages

2018 ◽  
Vol 11 (3) ◽  
pp. 81
Author(s):  
Aymeric Ousset ◽  
Rosanna Chirico ◽  
Florent Robin ◽  
Martin Schubert ◽  
Pascal Somville ◽  
...  
Keyword(s):  
Spray Drying ◽  
Drug Loading ◽  
Solid Dispersions ◽  
Physical Stability ◽  
Amorphous State ◽  
Amorphous Solid ◽  
Screening Strategy ◽  
Water Soluble ◽  
Small Scale ◽  
Absorption Window

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.

scholarly journals Development of a small-scale spray-drying approach for amorphous solid dispersions (ASDs) screening in early drug development

2018 ◽  
Vol 24 (5) ◽  
pp. 560-574 ◽  
Author(s):  
Aymeric Ousset ◽  
Céline Bassand ◽  
Pierre-François Chavez ◽  
Joke Meeus ◽  
Florent Robin ◽  
...  
Keyword(s):  
Drug Development ◽  
Spray Drying ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Small Scale ◽  
Amorphous Solid Dispersions ◽  
Early Drug

scholarly journals Development of a Surface Coating Technique with Predictive Value for Bead Coating in the Manufacturing of Amorphous Solid Dispersions

Pharmaceutics ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 878
Author(s):  
Eline Boel ◽  
Piyush Panini ◽  
Guy Van den Mooter
Keyword(s):  
Phase Behavior ◽  
Spray Drying ◽  
Surface Coating ◽  
Drug Loading ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Film Casting ◽  
Amorphous Solid Dispersions ◽  
Coating Technique ◽  
Amorphous System

The aim of this paper was to investigate whether a surface coating technique could be developed that can predict the phase behavior of amorphous solid dispersions (ASDs) coated on beads. ASDs of miconazole (MIC) and poly(vinylpyrrolidone-co-vinyl acetate) (PVP-VA) in methanol (MeOH) were studied as a model system. First, the low crystallization tendency of the model drug in MeOH was evaluated and confirmed. In a next step, a drug loading screening was performed on casted films and coated beads in order to define the highest possible MIC loading that still results in a one-phase amorphous system. These results indicate that film casting is not suitable for phase behavior predictions of ASDs coated on beads. Therefore, a setup for coating a solid surface was established inside the drying chamber of a spray dryer and it was found that this surface coating technique could predict the phase behavior of MIC-PVP-VA systems coated on beads, in case an intermittent spraying procedure is applied. Finally, spray drying was also evaluated for its ability to manufacture high drug-loaded ASDs. The highest possible drug loadings that still result in a one-phase amorphous system were obtained for bead coating and its predictive intermittent surface coating technique, followed by spray drying and finally by film casting and the continuous surface coating technique, thereby underlining the importance for further research into the underexplored bead coating process.

scholarly journals Bioavailability Improvement of Carbamazepine via Oral Administration of Modified-Release Amorphous Solid Dispersions in Rats

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1023
Author(s):  
Houli Li ◽  
Meimei Zhang ◽  
Lilong Xiong ◽  
Weiyi Feng ◽  
Robert O. Williams
Keyword(s):  
Controlled Release ◽  
Oral Absorption ◽  
Solid Dispersions ◽  
Amorphous State ◽  
Amorphous Solid ◽  
Water Soluble ◽  
Pharmacokinetic Studies ◽  
Modified Release ◽  
Capsule Formulation ◽  
Amorphous Solid Dispersions

The purpose of this study was to improve the bioavailability of carbamazepine (CBZ), a poorly water-soluble antiepileptic drug, via modified-release amorphous solid dispersions (mr-ASD) by a thin film freezing (TFF) process. Three types of CBZ-mr-ASD with immediate-, delayed-, and controlled-release properties were successfully prepared with HPMC E3 (hydrophilic), L100-55 (enteric), and cellulose acetate (CA, lipophilic), defined as CBZ-ir-ASD, CBZ-dr-ASD, and CBZ-cr-ASD, respectively. A dry granulation method was used to prepare CBZ-mr-ASD capsule formulations. Various characterization techniques were applied to evaluate the physicochemical properties of CBZ-mr-ASD and the related capsules. The drug remained in an amorphous state when encapsulated within CBZ-mr-ASD, and the capsule formulation progress did not affect the performance of the dispersions. In dissolution tests, the preparations and the corresponding dosage forms similarly showed typical immediate-, delayed-, and controlled-release properties depending on the solubility of the polymers. Moreover, single-dose 24 h pharmacokinetic studies in rats indicated that CBZ-mr-ASD significantly enhanced the oral absorption of CBZ compared to that of crude CBZ. Increased oral absorption of CBZ was observed, especially in the CBZ-dr-ASD formulation, which showed a better pharmacokinetic profile than that of crude CBZ with 2.63- and 3.17-fold improved bioavailability of the drug and its main active metabolite carbamazepine 10,11-epoxide (CBZ-E).

scholarly journals Applications of Dynamic Mechanical Analysis in the Engineering of Amorphous Solid Dispersions

2020 ◽  
Vol 02 (01) ◽  
pp. e55-e63
Author(s):  
Andrew Toye Ojo ◽  
Ping I. Lee
Keyword(s):  
Molecular Mobility ◽  
Solid Dispersions ◽  
Physical Stability ◽  
Amorphous Solid ◽  
Mechanical Analysis ◽  
Water Soluble ◽  
Amorphous Solid Dispersions ◽  
Poorly Water Soluble Drugs ◽  
Water Soluble Drugs ◽  
Poorly Water Soluble

AbstractDynamic mechanical analysis (DMA) offers several advantages over prevailing methods in the characterization of amorphous solid dispersions (ASDs) typically used for improving the delivery of poorly water-soluble drugs. This method of analysis, though underutilized in the study of pharmaceutical systems, is particularly attuned to rheological investigations of thermal and mechanical properties of solids such as ASDs. Its ability to determine the viscoelastic properties of systems across a wide range of temperatures and shear conditions provides useful insight for the development and processing of ASDs. The response of materials to an imposed stress, captured by DMA, can help identify proper conditions for preparing homogenous extrudates of the polymer and active pharmaceutical ingredient through hot melt extrusion (HME). As HME continues to gain utility within the pharmaceutical industry, the ability to tailor process conditions will become increasingly important for the efficient design and production of ASD products for poorly water-soluble drugs. Furthermore, DMA can be used to probe molecular mobility and its link to physical stability of ASDs. Establishing the link between molecular mobility and crystallization kinetics is central to predicting the physical stability of ASDs. Therefore, increasing the understanding of material properties through DMA will enable the successful development of more stable amorphous drug products. This review summarizes current characterization tools for ASDs and discusses the potential of utilizing DMA as a robust alternative to traditional methods.

scholarly journals Enhanced Dissolution Efficiency of Tamoxifen Combined with Methacrylate Copolymers in Amorphous Solid Dispersions

Crystals ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 1046
Author(s):  
Dayanne T. C. da Silva ◽  
Daniela Nadvorny ◽  
Lucas J. de A. Danda ◽  
Amanda C. Q. de M. Vieira ◽  
Patricia Severino ◽  
...  
Keyword(s):  
Drug Loading ◽  
Solid Dispersions ◽  
Amorphous State ◽  
Amorphous Solid ◽  
Physical Mixture ◽  
Polymer Mixture ◽  
Scanning Calorimetry ◽  
Amorphous Solid Dispersions ◽  
Acrylate Copolymer ◽  
Poorly Soluble

Amorphous solid dispersions (SDs) containing poorly soluble tamoxifen dispersed in a meth(acrylate) copolymer combination were proposed as a controlled release system. The objective of this work was to investigate the characteristics and performance of the tamoxifen–polymer mixture and evaluate the changes in functionality through a supersaturating dissolution study condition while comparing it to a physical mixture at a fixed drug-loading proportion. Two polymers, Eudragit® L 100 and Eudragit® RL 100, were used to prepare SDs with a 1:1 polymer ratio, containing 10%, 20%, or 30% (wt/wt%) of tamoxifen, by the solvent evaporation method. A physical mixture containing 30% of tamoxifen was also prepared for comparison. SDs were characterized by X-ray diffraction, Fourier-transform infrared spectroscopy, differential scanning calorimetry, and scanning electron microscopy. Dissolution tests were conducted under non-sink conditions to verify the occurrence of drug recrystallization upon its release. Solid-state characterizations confirmed that the drug was in the amorphous state within the polymeric matrix. Tamoxifen release in an acidic medium was mainly affected by the increase in drug concentration caused by the possible loss of interactions that characterize the main polymer functionalities. At pH 7.4, supersaturation was slowly achieved while also contributing to the increase in the kinetic solubility of the drug. The physical mixture demonstrated the best overall performance, suggesting that the polymeric interactions may have negatively affected the drug release. The combination of polymers in the composing SD proved to be a promising strategy to tailor the delivery of poorly soluble drugs. Our study highlights important information on the behavior of tamoxifen as a poorly soluble drug in supersaturating dissolution conditions while released from SD systems.

scholarly journals Preparation and Characterization of Artemether Solid Dispersion by Spray Drying Technique

2021 ◽  
Vol 11 (2) ◽  
pp. 1-5
Author(s):  
Dhiraj Dabhade ◽  
Kamlesh Wadher ◽  
Shrikant Bute ◽  
Nikita Naidu ◽  
Milind Umekar ◽  
...  
Keyword(s):  
Dissolution Rate ◽  
Spray Drying ◽  
Solid Dispersion ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Study Data ◽  
Water Soluble ◽  
Amorphous Solid Dispersion ◽  
Scanning Calorimetry ◽  
Poorly Water Soluble

Introduction: Artemether, a BCS class IV drug (poorly water soluble and poorly permeable, less bioavailability) but is found to be effective against falciparum malaria. Preparation of water soluble formulation could be the technique to improve bioavailability of such drug. The most ideally used technique to enhance the solubility and dissolution of poorly water soluble drugs is Solid dispersion method. Method: The objective of the study was to enhance the solubility and dissolution rate of Artemether by preparing solid dispersions using Soluplus, at different ration of 1:1, 1:2, 1:3 and 1:4 using spray drying technology. Prepared Solid dispersions were characterized by Fourier transform infrared spectroscopy and differential scanning calorimetry. Results: The spray-dried solid dispersions found to be having less crystallinity and showed higher dissolution rates. Solubility study data showed the optimum drug/Soluplus ratio to be 1:3. The dissolution studies of Solid dispersions in 1.2 pH and 6.8 pH buffer showed higher drug release as compared to pure drug. Conclusion: Thus we conclude that an amorphous solid dispersion of Artemether could be a better option for enhancing the dissolution rate of drug Keywords: solid dispersion, artemether, soluplus, solubility enhancement

scholarly journals Recent Technologies for Amorphization of Poorly Water-Soluble Drugs

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1318
Author(s):  
Do-Hyun Kim ◽  
Young-Woo Kim ◽  
Yee-Yee Tin ◽  
Mya-Thet-Paing Soe ◽  
Byoung-Hyen Ko ◽  
...  
Keyword(s):  
Energy State ◽  
Drug Loading ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
High Energy ◽  
Water Soluble ◽  
Poorly Water Soluble Drugs ◽  
Preparation Methods ◽  
Water Soluble Drugs ◽  
Poorly Water Soluble

Amorphization technology has been the subject of continuous attention in the pharmaceutical industry, as a means to enhance the solubility of poorly water-soluble drugs. Being in a high energy state, amorphous formulations generally display significantly increased apparent solubility as compared to their crystalline counterparts, which may allow them to generate a supersaturated state in the gastrointestinal tract and in turn, improve the bioavailability. Conventionally, hydrophilic polymers have been used as carriers, in which the amorphous drugs were dispersed and stabilized to form polymeric amorphous solid dispersions. However, the technique had its limitations, some of which include the need for a large number of carriers, the tendency to recrystallize during storage, and the possibility of thermal decomposition of the drug during preparation. Therefore, emerging amorphization technologies have focused on the investigation of novel amorphous-stabilizing carriers and preparation methods that can improve the drug loading and the degree of amorphization. This review highlights the recent pharmaceutical approaches utilizing drug amorphization, such as co-amorphous systems, mesoporous particle-based techniques, and in situ amorphization. Recent updates on these technologies in the last five years are discussed with a focus on their characteristics and commercial potential.

AMORPHOUS SOLID DISPERSIONS OF PIOGLITAZONE HYDROCHLORIDE USING CREMOPHOR RH 40 AND POLOXAMER 188: IN VITRO AND IN VIVO EVALUATION

INDIAN DRUGS ◽  
2019 ◽  
Vol 56 (01) ◽  
pp. 45-55
Author(s):  
R. P Swain ◽  
B. B Subudhi ◽  
Keyword(s):  
Solid Dispersions ◽  
Amorphous State ◽  
Amorphous Solid ◽  
Water Soluble ◽  
Amorphous Solid Dispersions ◽  
In Vivo Evaluation ◽  
In Vivo Test ◽  
Water Soluble Drug

The study was aimed to improve dissolution and bioavailability of developed stable amorphous solid dispersions (SDs) of pioglitazone hydrochloride (PGH), a poorly water soluble drug. TGA showed compatibility with the polymers. The significant change in melting pattern of the PGH observed in the DSC thermograms supported by XRD patterns and SEM indicated change from crystalline to amorphous state. Prevention of recrystallization during storage suggested stability of formulation. Cremophor RH 40 based SD (solvent method) remarkably increased the dissolution within 15 min and was supported by dissolution parameters (Q15, IDR, RDR, % DE, f1, f2). In vivo test showed significantly (p < 0.05) higher AUC0-t and Cmax, which were about 4.46 and 4.84 times that of pure drug, respectively. Cremophor RH 40 was found to be a suitable carrier for SM for preparation of SDs of PH as evident from increased dissolution and bioavailability.

scholarly journals Micro-Injection Moulding of Poly(vinylpyrrolidone-vinyl acetate) Binary and Ternary Amorphous Solid Dispersions

Pharmaceutics ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 240
Author(s):  
Romina Pezzoli ◽  
Michael Hopkins Jnr ◽  
Guillaume Direur ◽  
Noel Gately ◽  
John G. Lyons ◽  
...  
Keyword(s):  
Vinyl Acetate ◽  
Injection Moulding ◽  
Solid Dispersions ◽  
Amorphous State ◽  
Amorphous Solid ◽  
Water Soluble ◽  
Drug Dissolution ◽  
Dissolution Profile ◽  
Amorphous Solid Dispersions ◽  
Micro Injection Moulding

Micro-injection moulding (µIM) was used for the production of enteric tablets of plasticised and unplasticised solid dispersions of poly(vinylpyrrolidone-vinyl acetate) (PVPVA), and the effect of the mechanical and thermal treatment on the properties of the dispersions was investigated. The physical state of the systems showed to be unaltered by the µIM step, maintaining the drug in the amorphous state. The dissolution profile of the tablets showed a slower dissolution rate due to the lower surface to volume ratio compared to the extruded strands. The lack of solubility of the doses in the acidic medium as a consequence of the acidity of indomethacin (IND) was observed. However, in neutral pH the drug dissolution showed slower rates without affecting the dissolution extent, showing a potential application for the development of controlled release doses. Overall, the production of tablets of amorphous solid dispersions (ASD), coupling hot-melt extrusion (HME) and µIM, proved to be a successful approach towards a continuous automated manufacturing process to improve the aqueous solubility of poorly water-soluble drugs.

scholarly journals Generation of high drug loading amorphous solid dispersions by Spray Drying

2018 ◽  
Author(s):  
Bhianca Lins de Azevedo Costa ◽  
Martial Sauceau ◽  
Romain Sescousse ◽  
Maria Ines Re
Keyword(s):  
Spray Drying ◽  
Drug Carrier ◽  
Drug Loading ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Amorphous Solid Dispersion ◽  
Drug Solubility ◽  
Amorphous Solid Dispersions ◽  
High Drug ◽  
High Drug Loading

Amorphous solid dispersions (ASDs) refers to drug - carrier systems, where the drug is dispersed in the carrier at a molecular level. In this work, ASDs were formulated by spray drying. The aim was to achieve high drug loads of an amorphous hydrophobic drug (Efavirenz - EFV) in  the  carrier Soluplus®. Solid state characterizations (mDSC, XRPD, DVS, Raman, SEM, stability and solubility studies) were done. EFV amorphisation in ASDs (20 to 85% EFV loads) resulted in improved drug solubility compared to unprocessed EFV crystals and tendency of properties evolution over time for ASDs with EFV loads  higher than 70 wt%. Keywords: amorphous solid dispersion, spray drying, high drug loading, soluplus, efavirenz.

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