Thesis work- A large fraction of the drug candidates under development are characterized by very poor aqueous solubility. The pharmaceutical community is increasing its attention on the amorphous state of numerous pharmaceuticals wherein the crystalline state, in light of the poor aqueous solubility, will not deliver the desired drug concentration into the systemic circulation. However, the amorphous state can confer both physical and chemical instability. Thus, the effective use of these amorphous compounds requires the ability to predict their stability. The overall objective of my research is to build correlation models which can be used to predict the stability of amorphous materials both in single and multi-component systems.
Molecular mobility, in light of its potential correlation to physical stability, has been recognized as a key factor in the stabilization of amorphous materials. Molecular mobility encompasses both global (cooperative motion of many molecules) and local motions (non-cooperative motions arising from individual molecules). We are evaluating the relationship between different molecular motions and various important properties related to the stability of amorphous pharmaceuticals including crystallization and water sorption. Dielectric spectroscopy is the primary technique that we use to study different types of molecular relaxations in model amorphous compounds. Also, we seek to gain mechanistic insights into the effect of different preparation methods and addition of different additives on the stability of the amorphous form produced.
The widespread and effective use of amorphous pharmaceuticals hinges on our ability to accurately predict their stability under a variety of storage conditions and in complex multi-component matrices. Since the drug approval process is increasingly becoming science-based, the regulatory bodies (e.g., FDA in the United States) will base their decision on such information.
Other projects- We are also involved in various material characterization and solid-state transformation studies:
FT-Raman spectroscopy, although generally used as a complementary technique, presents some unique advantages including rapid and non-destructive nature and minimum interference from water which make it amenable to the analysis of intact dosage forms. We have used FT-Raman spectroscopy to identify the physical form and also follow the solid-state phase transformations in intact trehalose tablets.
Interaction with water can bring about various pharmaceutically relevant and often unintended changes in the physical form of both active as well as excipients. We have been able to identify a new polymorphic form of an active pharmaceutical ingredient (API) by deliberate variation in the resistance to water removal from its dihydrate. It was shown that the different levels of interaction with water could lead to different solid forms after dehydration. Moreover, variable temperature powder x-ray diffractometry (XRD) and differential scanning calorimetry (DSC) was used to characterize the new form as well as successfully show the sequential formation of different polymorphs on dehydration.
Contract work- Our group is also involved in carrying out contract work wherein we work on some of the industrial problems and also do some material characterization studies for different pharmaceutical companies. We have carried out water sorption studies of a macromolecule in the development stage to characterize its water sorption behavior at different RH conditions. This type of information is very important for the development of an effective formulation and its subsequent storage. We have also been involved in some preformulation studies where we are trying to characterize the hydrate to anhydrate inter-conversion in a proprietary molecule.
1. S. P. Bhardwaj, R. Suryanarayanan. Subtraction of dc conductivity and annealing - approaches to identify Johari-Goldstein relaxation in amorphous trehalose. Molecular Pharmaceutics, 8 (2011), 1416-1422.
2. P. Chakravarty, S.P. Bhardwaj, L. King, R. Suryanarayanan. Monitoring phase transformations in intact tablets of trehalose by FT-Raman spectroscopy. AAPS PharmSciTech, 10 (2009), 1420-1426.
3. S.P. Bhardwaj, S. Singh. Study of forced degradation behavior of enalapril maleate by LC and LC-MS and development of a validated stability-indicating assay method. Journal of Pharmaceutical and Biomedical Analysis, 46 (2008), 113-120.
4. C. Passey, S.P. Bhardwaj, D.K. Majumdar. Is Relief from Diabetes Just a Breath Away...? Current Drug Delivery, 6 (2009), 166-173.
1. S. P. Bhardwaj, R. Suryanarayanan. "Effect of preparation method on molecular mobility in amorphous trehalose - implications on physical stability". Poster presentation, AAPS annual meeting, Washington, DC, October 2011.
2. S. P. Bhardwaj, R. Suryanarayanan. "Effect of water sorption on molecular mobility in amorphous trehalose". Poster presentation, AAPS annual meeting, Washington, DC, October 2011.
3. S. P. Bhardwaj, R. Suryanarayanan. "Two methods of thermal history removal in amorphous trehalose - effect on molecular mobility". Poster presentation, AAPS annual meeting, Washington, DC, October 2011.
4. K. Arora, S. P. Bhardwaj, R. Suryanarayanan. "A new polymorph of adefovir dipivoxil obtained by controlled dehydration of its dehydrate". Poster presentation, AAPS annual meeting, Washington, DC, October 2011.
5. "Use of broadband dielectric spectroscopy to predict the water sorption potential of amorphous pharmaceuticals". Graduate student symposium award presentation in APQ section at AAPS annual meeting, New Orleans, November 2010.
6. S. P. Bhardwaj, B. L. Givot, R. Suryanarayanan. "Use of broadband dielectric spectroscopy to predict the water sorption potential of amorphous pharmaceuticals". Poster presentation, AAPS annual meeting, New Orleans, November 2010.
7. S. P. Bhardwaj, B. L. Givot, R. Suryanarayanan. "Global molecular mobility in amorphous trehalose and the effect of annealing". Poster presentation, AAPS annual meeting, New Orleans, November 2010.
8. S. P. Bhardwaj, B. L. Givot, R. Suryanarayanan. "Effect of annealing on local mobility of trehalose". Poster presentation, AAPS annual meeting, Los Angeles, November 2009.
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