Research Proposal for PhD Admission

Project Title:

Solid State Characterization, Phase solubility/miscibility and drug-rich phase formation on the
performance of co-amorphous materials.

Proposed Mode of Research:

The proposed Research study was designed to investigate the contribution of solid-state and
the impact of composite drug-rich phase generated because of pH shift on the maximum
achievable super saturation of co-amorphous formulations. The co-amorphous phases of weak
base-weak base pair will be prepared in anticipation of studying the effect of drug-rich phase
consequent to pH shift. While the co-amorphous phases of weak base-Weak acid pair will be
prepared to understand the manifestation of the solid-state drug: co-former miscibility in the
absence of drug rich phase. In addition, the Thermodynamic Studies will also be studied for
super saturation state.

Aims & Objectives:

Co-amorphous formulations are becoming alternatives to solid dispersion technology. Unlike
polymeric solid dispersions, co-amorphous formulations employ small molecular weight
compounds as co-formers, which result in better stability, high drug loading, and improved
performance. Drug-Co-former miscibility/solubility is a prerequisite for a stable co-amorphous
system formation; such miscibility/solubility has thermodynamic and kinetic consequences on
the performance of the co-amorphous systems.

Literature Review & Research Gap:

When both weak basic drugs are used to form a co-amorphous material during the pH shift
studies Liquid Liquid Phase Separation (LLPS) is formed which reduces the amorphous
solubility of drugs which leads to formation of colloidal drug rich phase. As a result,
thermodynamically activity of each drug in co-amorphous material membrane transport is
reduced. Therefore, to overcome LLPS formation, weak basic drugs is combined with weak
acids for improved solubility and stability. Weak acids increases the solubility of weak basic
drugs by enhancing the solid-state characterization of weak basic drugs. Weak acids also
increases the permeability simultaneously by enhancing the drug miscible phase.

Proposed Methodology:
1. Selection of Drugs
2. Preparation of Co-Amorphous Materials
3. Solid State Characterization
4. Solubility Determination
5. Permeability Determination
6. Thermodynamic Studies
 Research Proposal for PhD Admission
Bibliography:
1. Alhalaweh, A., Bergstr¨om, C.A.S., Taylor, L.S., 2016. Compromised in vitro
dissolution and membrane transport of multidrug amorphous formulations. J. Control.
Release 229, 172–182.

2. Chavan, R.B., Thipparaboina, R., Kumar, D., Shastri, N.R., 2016. Co amorphous
systems: A product development perspective. Int. J. Pharm. 515 (1-2), 403–415.

3. Chegireddy, M., Hanegave, G.K., Lakshman, D., Urazov, A., Sree, K.N., Lewis, S.A.,
Dengale, S.J., 2020. The Significance of Utilizing In Vitro Transfer Model and Media
Selection to Study the Dissolution Performance of Weak Ionizable Bases: Investigation
Using Saquinavir as a Model Drug. AAPS PharmSciTech 21 (2).

4. El-Badry, M., Fetih, G., Fathy, M., 2009. Improvement of solubility and dissolution
rate of indomethacin by solid dispersions in Gelucire 50/13 and PEG4000. Saudi
Pharm. J. 17 (3), 217–225.

5. Fedors, R.F., 1974. A method for estimating both the solubility parameters and molar
volumes of liquids. Polym. Eng. Sci. 14 (2), 147–154.