- Post Doctoral
MIT Unit Affiliation:
- Chemical Engineering
Post Doc Sponsor / Advisor:
Date PhD Completed:
Top 3 Areas of Expertise:
Expected End Date of Post Doctoral Position:
Continuous pharmaceutical downstream manufacturing by innovative technologies
- Evaluated hot-melt extrusion, injection molding and other novel processes to develop and translate technologies for the manufacture of pharmaceuticals (particularly, tablets) in a continuous mode.
Innovations in processing of pharmaceuticals
- Handled pharmaceutical engineering projects related to granulation, milling, tabletting and solubility enhancement of poorly soluble active pharmaceutical ingredients (APIs).
Study of disintegrants and disintegration phenomena
- Developed a visiometric technique to study functionalities of disintegrants by high-speed video imaging.
- Characterized energy and heat changes occurred during disintegration process by solution calorimetry.
- Designed a novel disintegration apparatus to evaluate disintegration of rapidly disintegrating tablets (RDTs).
- Identified optimized blends of disintegrants by Design of Experiments (DoE) study and implemented Quality by Design (QbD) paradigm to formulate RDTs by direct compression technology.
This study was centred on investigating the action of disintegrants and their roles in rapidly disintegrating tablets (RDTs) by visiometric, calorimetric, computational fluid dynamics (CFD) and quality by design (QbD) approaches.
The first part of this study reports the use of high-speed video imaging to visualise and elucidate the mechanisms of action of disintegrants when incorporated into compacts and as free disintegrant particles. Acquired images were processed using MATLAB and changes in the compact area and instantaneous motion of compacted particles on contact with water were analysed. The capillary action of compacts was determined for various disintegrants. The break-up behaviour of compacts prepared at different compression pressure with selected disintegrants was also analysed. The results from this visualisation study provided an in-depth understanding of the disintegrant behaviour of free and compacted disintegrant particles upon wetting. The mechanisms of swelling, capillary action, disruption of particle-particle bonds and strain recovery were successfully monitored. Solution calorimetry was also employed to further evaluate the heat of interaction phenomena of disintegrants. This particular study confirmed that all disintegrants are exothermic in nature. Also, structural and constitutional properties of disintegrants have direct effects on their enthalpy values.
In the second part of the study, disintegration test apparatus, particularly suitable for RDTs were developed. The designed RDT disintegration apparatus consisted of disintegration compartment, stereomicroscope and video camera. CFD was used to simulate different designs of the compartment. The simulation was validated to be in good agreement with the experimental results. Disintegration times of RDTs were determined using the designed RDT disintegration apparatus (I and II) and the USP disintegration apparatus. The results obtained using the designed apparatus (I and II) correlated well with those obtained by the USP disintegration apparatus. Thus, the applied CFD approach had the potential to predict the fluid hydrodynamics for the design of an optimal disintegration apparatus. The designed visiometric liquid jet-mediated disintegration apparatus for RDTs provided efficient and precise determination of very short disintegration times of rapidly disintegrating dosage forms.
In the last part of the study, functionality of disintegrants and their mixtures in RDTs were evaluated by a QbD approach. Ascorbic acid, aspirin and ibuprofen, which differ in water solubility, were chosen as the drug models. Disintegration time and hardness of RDTs were determined and modelled by using combined optimal design. The generated models were validated and used for further analysis. Graphical optimisation analysis demonstrated that the RDTs with desired disintegration times and hardness can be formulated with a larger area of design space by combining disintegrants at difference compression pressures. QbD is an efficient and effective paradigm in understanding formulation and process parameters and building quality into RDT systems.
In summary, findings of this PhD project expanded the understanding of the properties of disintegrants and RDTs.
Top 5 Awards and honors (name of award, date received):
5 Recent Papers:
Desai PM, Liew CV, Heng PWS. Understanding disintegrant action by visualization (2012). Journal of Pharmaceutical Sciences. 101 (6): 2155–2164
Desai PM, Liew CV, Heng PWS. Assessment of disintegration of rapidly disintegrating tablets by a visiometric liquid jet-mediated disintegration apparatus (2013). International Journal of Pharmaceutics. 442 (1–2): 65-73
Desai PM, Er XHP, Liew CV, Heng PWS. Functionality of disintegrants and disintegrant mixtures in enhancing fast disintegration of rapidly disintegrating tablets by a quality by design approach (2014). AAPS PharmSciTech. 15 (5): 1093-1104
Desai PM, Tan BMJ, Liew CV, Chan LW, Heng PWS. Impact of electrostatics on processing and product performance of pharmaceutical solids (2015). Current Pharmaceutical Design. 21 (40): 5923-5929
Desai PM, Vaerenbergh GV, Holman J, Liew CV, Heng PWS. Continuous manufacturing: the future in pharmaceutical solid dosage form manufacturing (2015). Pharmaceutical Bioprocessing. 3 (5): 357-360
Desai PM, Liew CV, Heng PWS. Review of Disintegrants and the Disintegration Phenomena (2016). Journal of Pharmaceutical Sciences. Article in press
Heng PWS, Desai PM, Liew CV. Apparatus and method for visiometric disintegration. US Patent Application No: 14/249854, Publication No: US 2014/0305225 A1, Filing date: April 10, 2014, Publication date: October 16, 2014.