scholarly journals The Investigation of Flory–Huggins Interaction Parameters for Amorphous Solid Dispersion Across the Entire Temperature and Composition Range

Pharmaceutics ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 420 ◽  
Author(s):  
Yiwei Tian ◽  
Kaijie Qian ◽  
Esther Jacobs ◽  
Esther Amstad ◽  
David S. Jones ◽  
...  
Keyword(s):  
Solid Dispersion ◽  
Water Solubility ◽  
Composition Range ◽  
Amorphous Polymer ◽  
Drug Loading ◽  
Amorphous Solid ◽  
Interaction Parameters ◽  
Amorphous Solid Dispersion ◽  
Amorphous Drug ◽  
The Relationship

Amorphous solid dispersion (ASD) is one of the most promising enabling formulations featuring significant water solubility and bioavailability enhancements for biopharmaceutical classification system (BCS) class II and IV drugs. An accurate thermodynamic understanding of the ASD should be established for the ease of development of stable formulation with desired product performances. In this study, we report a first experimental approach combined with classic Flory–Huggins (F–H) modelling to understand the performances of ASD across the entire temperature and drug composition range. At low temperature and drug loading, water (moisture) was induced into the system to increase the mobility and accelerate the amorphous drug-amorphous polymer phase separation (AAPS). The binodal line indicating the boundary between one phase and AAPS of felodipine, PVPK15 and water ternary system was successfully measured, and the corresponding F–H interaction parameters (χ) for FD-PVPK15 binary system were derived. By combining dissolution/melting depression with AAPS approach, the relationship between temperature and drug loading with χ (Φ, T) for FD-PVPK15 system was modelled across the entire range as χ = 1.72 − 852/T + 5.17·Φ − 7.85·Φ2. This empirical equation can provide better understanding and prediction for the miscibility and stability of drug-polymer ASD at all conditions.

scholarly journals Evaluating the effect of the porous and non-porous colloidal silicon dioxide as a stabilizer on amorphous solid dispersion

2020 ◽  
Vol 10 (5) ◽  
pp. 255-263
Author(s):  
Smruti P. Chaudhari ◽  
Mittal Bhadiyadra ◽  
Rutesh H. Dave
Keyword(s):  
Silicon Dioxide ◽  
Dissolution Rate ◽  
Solid Dispersion ◽  
Water Solubility ◽  
High Surface ◽  
Amorphous Solid ◽  
Energy System ◽  
High Energy ◽  
Amorphous Solid Dispersion ◽  
The Stability

Advancement in the discovery of drugs has led to many highly lipophilic compounds with very low water solubility. Amorphous solid dispersion is one of the emerging technologies to increase the solubility of these drugs. The stability of these systems is critical since the high energy system tends to recrystallize, which negates the benefits of these systems. In this paper, we are evaluating the use of colloidal silicon dioxide as a potential stabilizer to stabilize the amorphous solid dispersions. Two types of colloidal silicon dioxide are used: porous colloidal silicon dioxide -Syloid 244 Fp and nonporous fumed silica – Aerosil 200. These silicon dioxides have a high surface area. Two methods of incorporation are used to incorporate silicon dioxide into the solid dispersion. The spray drying method is used to make amorphous solid dispersion. It was found that porous silicon dioxide is better to increase stability as well as increasing dissolution rate and % release of the drug. The addition of silicon dioxide internally to the dispersion increases the dissolution rate, and the addition of silicon dioxide externally increases the stability of the solid dispersion. Keywords: colloidal silicon dioxide, stabilizer, amorphous solid dispersion, low water solubility

scholarly journals Aqueous and pH dependent coacervation method for taste masking of paracetamol via amorphous solid dispersion formation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Basheer Al-kasmi ◽  
M. H. D. Bashir Alsirawan ◽  
Anant Paradkar ◽  
Abdul-Hakim Nattouf ◽  
Hind El-Zein
Keyword(s):  
Solid Dispersion ◽  
Drug Loading ◽  
Amorphous Solid ◽  
Industrial Applications ◽  
Taste Masking ◽  
Amorphous Solid Dispersion ◽  
Peg 400 ◽  
Low Viscosity ◽  
Ph Dependent ◽  
Ph Level

AbstractTaste masking of paracetamol was achieved by preparing amorphous solid dispersion (ASD) using modified coacervation method. The method is based on dissolving the drug and polymeric carrier in water adjusted to certain pH level. Then, precipitation of ASD granules is performed by gradually changing pH level. Therefore, the chosen drug and polymer should obtain appropriate acidic or basic groups to enable pH-dependent solvation. Moreover, using solubility enhancing additives such as sodium lauryl sulphate (SLS) and low viscosity polyethylene glycol (PEG 400) found to be essential in aiding drug/polymer aqueous solvation which enhanced amorphization, hence taste masking and drug loading. Solid dispersion between Paracetamol and Eudragit E was formed and that proved by FT-IR, DSC, PXRD and SEM. Also, Paracetamol was released after 2 min in 0.1 N hydrochloric acid medium and the taste of masking forms are accepted from all volunteers. Modified coacervation method does not involve organic solvents, high temperatures, or sophisticated instruments commonly used in taste masking methods. Using PEG 400 resulted in significantly higher drug loading and dissolution rate compared to SLS granules. Moreover, using previously reported scoring system for the evaluation of taste masking methods shows that pH dependent coacervation obtained high scoring over common methods and thus display a robust potential for industrial applications.

scholarly journals Applicability of an Experimental Grade of Hydroxypropyl Methylcellulose Acetate Succinate as a Carrier for Formation of Solid Dispersion with Indomethacin

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 353
Author(s):  
Hiroshi Ueda ◽  
Yuya Hirakawa ◽  
Hironori Tanaka ◽  
Tetsuya Miyano ◽  
Katsuji Sugita
Keyword(s):  
Solid Dispersion ◽  
Hydroxypropyl Methylcellulose ◽  
Principal Component ◽  
Amorphous Solid ◽  
Water Soluble ◽  
Amorphous Solid Dispersion ◽  
Scanning Calorimetry ◽  
Water Soluble Drugs ◽  
Poorly Water Soluble ◽  
Amorphous Drug

The transformation of a crystalline drug into an amorphous form is a promising way to enhance the oral bioavailability of poorly water-soluble drugs. Blending of a carrier, such as a hydrophilic polymer, with an amorphous drug is a widely used method to produce a solid dispersion and inhibit crystallization. This study investigates an experimental grade of hydroxypropyl methylcellulose acetate succinate, HPMCAS-MX (MX), as a solid dispersion carrier. Enhancement of thermal stability and reduction of the glass transition temperature (Tg) of MX compared with those of the conventional grade were evaluated through thermogravimetric analysis and differential scanning calorimetry (DSC). The formation of a homogeneous amorphous solid dispersion between MX and indomethacin was confirmed by X-ray powder diffraction analysis, DSC, and Raman mapping. It was observed that 10–30% MX did not act as an anti-plasticizer, but the utilization of >40% MX caused an increase in Tg and reduction of molecular mobility. This could be explained by a change in intermolecular interactions, inferred from infrared spectroscopy combined with principal component analysis. HPMCAS-MX exhibited similar performance to that of conventional-grade, HPMCAS-MG. Although HPMCAS-MX has thermal properties different from those of conventional-grade HPMCAS-MG, it retains its ability as a solid dispersion carrier.

Impact of Drug-Polymer Interaction in Amorphous Solid Dispersion Aiming for the Supersaturation of Poorly Soluble Drug in Biorelevant Medium

2020 ◽  
Vol 21 (5) ◽  
Author(s):  
Cassiana Mendes ◽  
Rafael G. Andrzejewski ◽  
Juliana M. O. Pinto ◽  
Leice M. R. de Novais ◽  
Andersson Barison ◽  
...  
Keyword(s):  
Solid Dispersion ◽  
Amorphous Solid ◽  
Amorphous Solid Dispersion ◽  
Poorly Soluble ◽  
Poorly Soluble Drug ◽  
Drug Polymer Interaction ◽  
Biorelevant Medium ◽  
Polymer Interaction

scholarly journals Amorphous Solid Dispersion Tablets Overcome Acalabrutinib pH Effect in Dogs

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 557
Author(s):  
Deanna M. Mudie ◽  
Aaron M. Stewart ◽  
Jesus A. Rosales ◽  
Nishant Biswas ◽  
Molly S. Adam ◽  
...  
Keyword(s):  
Solid Dispersion ◽  
Drug Exposure ◽  
Ph Effect ◽  
Hydroxypropyl Methylcellulose ◽  
Amorphous Solid ◽  
Gastric Ph ◽  
Patient Treatment ◽  
Oral Exposure ◽  
Amorphous Solid Dispersion ◽  
Plasma Drug

Calquence® (crystalline acalabrutinib), a commercially marketed tyrosine kinase inhibitor (TKI), exhibits significantly reduced oral exposure when taken with acid-reducing agents (ARAs) due to the low solubility of the weakly basic drug at elevated gastric pH. These drug–drug interactions (DDIs) negatively impact patient treatment and quality of life due to the strict dosing regimens required. In this study, reduced plasma drug exposure at high gastric pH was overcome using a spray-dried amorphous solid dispersion (ASD) comprising 50% acalabrutinib and 50% hydroxypropyl methylcellulose acetate succinate (HPMCAS, H grade) formulated as an immediate-release (IR) tablet. ASD tablets achieved similar area under the plasma drug concentration–time curve (AUC) at low and high gastric pH and outperformed Calquence capsules 2.4-fold at high gastric pH in beagle dogs. In vitro multicompartment dissolution testing conducted a priori to the in vivo study successfully predicted the improved formulation performance. In addition, ASD tablets were 60% smaller than Calquence capsules and demonstrated good laboratory-scale manufacturability, physical stability, and chemical stability. ASD dosage forms are attractive for improving patient compliance and the efficacy of acalabrutinib and other weakly basic drugs that have pH-dependent absorption.

scholarly journals Drug-Rich Phases Induced by Amorphous Solid Dispersion: Arbitrary or Intentional Goal in Oral Drug Delivery?

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 889
Author(s):  
Kaijie Qian ◽  
Lorenzo Stella ◽  
David S. Jones ◽  
Gavin P. Andrews ◽  
Huachuan Du ◽  
...  
Keyword(s):  
Solid Dispersion ◽  
Oral Drug Delivery ◽  
Drug Product ◽  
Amorphous Solid ◽  
Water Soluble ◽  
Nucleation Theory ◽  
Product Development Process ◽  
Classical Nucleation Theory ◽  
Oral Drug ◽  
Amorphous Solid Dispersion

Among many methods to mitigate the solubility limitations of drug compounds, amorphous solid dispersion (ASD) is considered to be one of the most promising strategies to enhance the dissolution and bioavailability of poorly water-soluble drugs. The enhancement of ASD in the oral absorption of drugs has been mainly attributed to the high apparent drug solubility during the dissolution. In the last decade, with the implementations of new knowledge and advanced analytical techniques, a drug-rich transient metastable phase was frequently highlighted within the supersaturation stage of the ASD dissolution. The extended drug absorption and bioavailability enhancement may be attributed to the metastability of such drug-rich phases. In this paper, we have reviewed (i) the possible theory behind the formation and stabilization of such metastable drug-rich phases, with a focus on non-classical nucleation; (ii) the additional benefits of the ASD-induced drug-rich phases for bioavailability enhancements. It is envisaged that a greater understanding of the non-classical nucleation theory and its application on the ASD design might accelerate the drug product development process in the future.

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