Ternary Amorphous Solid Dispersions
Received Date: Oct 27, 2017 / Accepted Date: Nov 01, 2017 / Published Date: Nov 08, 2017
Keywords: Poorly soluble drugs; Amorphous; Physicochemical
Amorphous solid dispersion is one of the techniques used in the formulation development of poorly soluble compounds. Due to the advancement in basic physicochemical understanding of amorphous systems, the utilization of this techniques has immensely increased in enabling the delivery of the difficult to solubilize compounds. Traditional binary solid dispersions contain a drug dispersed in a single polymer matrix, whereas in recently developed ternary solid dispersions three components i.e., API, polymer, and an additive are present [1-7].
In both the systems, API is present in amorphous form and polymer is used for the stabilization of this amorphous form via decrease in molecular mobility or via drug-polymer molecular interactions. The third component is usually a surface-active agent or another polymer depending on the desired dissolution/stability profiles of the drug. For example, if the faster dissolution is desired then surfactant would be a better choice and if the prevention of re-crystallization is needed then another polymer with higher Tg may be used in developing the ternary solid dispersions.
One of the challenges associated with developing ternary dispersion is the selection of appropriate polymers/surfactant and their combinations. In those cases, solution studies can be successfully used to distinguish the ability of individual polymer vs. combined polymers for synergistic effect in terms of dissolution enhancement or amorphous stabilization or both . The parameters studied in such solution state screening studies usually are the ability of polymers or their combinations to inhibit precipitation and maintaining supersaturation (Figure 1).
The prepared ternary solid dispersions can be characterized by technique such as DSC/MDSC, PXRD, and FTIR. These techniques are used to determine important parameters such as the glass-transition temperature of amorphous components, the crystallinity of the drug and the molecular interaction between drug and excipients.
The future research focusing on the 1) combination of polymers to tailor the release profile and stability, 2) advance characterization techniques such as small angle X-ray scattering and solid-state NMR and 3) improvement in manufacturing of amorphous solid dispersions will progress the application of ternary solid dispersions strategy in resolving the challenges of current drug development program. The advancement of dedicated CROs for amorphous dispersions development and recent success of drugs such as Telaprevir (Incivek®) and Ivacaftor (Kalydeco®) suggests that this technique is capable of providing the desired approach for the development of poorly soluble compounds.
Finally, the fact that almost 40% of the new chemical entities are poorly water soluble in nature implies that studies with ternary solid dispersions will continue, and with increase understanding of these systems, more drug compounds formulated as solid dispersions will reach the market in the future.
- Prasad D, Chauhan H, Atef E (2014) Amorphous stabilization and dissolution enhancement of amorphous ternary solid dispersions: combination of polymers showing drug–polymer interaction for synergistic effects. Journal of Pharmaceutical Sciences 103: 3511-3523.
- Prasad D, Chauhan H, Atef E (2016) Role of molecular interactions for synergistic precipitation inhibition of poorly soluble drug in supersaturated drug–polymer–polymer ternary solution. Molecular Pharmaceutics 13: 756-765.
- Meng F, Dave V, Chauhan H (2015) Qualitative and quantitative methods to determine miscibility in amorphous drug–polymer systems. European Journal of Pharmaceutical Sciences 77: 106-111.
- Meng F, Gala U, Chauhan H (2015) Classification of solid dispersions: correlation to (i) stability and solubility (ii) preparation and characterization techniques. Drug Development and Industrial Pharmacy 41: 1401-1415.
- Meng F, Trivino A, Prasad D, Chauhan H (2015) Investigation and correlation of drug polymer miscibility and molecular interactions by various approaches for the preparation of amorphous solid dispersions. European Journal of Pharmaceutical Sciences 71: 12-24.
- Chauhan H, Kuldipkumar A, Barder T, Medek A, Gu CH, et al. (2014) Correlation of inhibitory effects of polymers on indomethacin precipitation in solution and amorphous solid crystallization based on molecular interaction. Pharmaceutical Research 31: 500-515.
- Chauhan H, Hui-Gu C, Atef E (2013) Correlating the behavior of polymers in solution as precipitation inhibitor to its amorphous stabilization ability in solid dispersions. Journal of Pharmaceutical Sciences 102: 1924-1935.
Citation: Prasad D, Lande J, Chauhan H, Chauhan H (2017) Ternary Amorphous Solid Dispersions. J Develop Drugs 6:181. Doi: 10.4172/2329-6631.1000181
Copyright: © 2017 Prasad D, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Select your language of interest to view the total content in your interested language
Share This Article
- Total views: 582
- [From(publication date): 0-2017 - May 27, 2018]
- Breakdown by view type
- HTML page views: 529
- PDF downloads: 53