The research work described in this thesis, the environmentally
friendly novel "Microwave Assisted Sub-Critical water (MASCW)" technology
for particle engineering of active pharmaceutical ingredients and excipients
was developed. The present novel technology MASCW process is described
as green technology as water is used as the solvent medium and microwave
energy as external source of heat energy for generation of a particle with
different morphological and chemical properties.
In MASCW process supersaturated solution of APIs is prepared by
dissolving solute in water at high temperature and pressure conditions. Upon
rapid and controlled cooling, based on the aqueous solubility of solute,
solute/solvent concentration and dielectric constant of water rapid
precipitation of API with narrow particle size distribution occurs.
Using paracetamol (pca) as API moiety understanding of the
mechanism of MASCW crystallisation process was investigated. The effect
of different process and experimental parameters on crystallisation pathway
and end product attributes were analysed. Correlation between the degree of
supersaturation concentration of pca solution against temperature and
pressure parameters was explained by generating binary phase diagram.
Determination of polymorphic transformation pathway of pca from form I
(stable) to form II metastable polymorphs in solution was analysed using Raman spectroscopy. The difference between conventional heating and
subcritical treatment was explored by determining the change in the solvent
dielectric constant and solubility of hydrophobic API molecule.
Based on the process understanding results, this technology was
further implemented to explore its application in generating phase pure
stable and metastable cocrystal phase. Based on the solubility of API and
cocrystal former congruent (CBZ/SAC, SMT/SAC, SMZ/SAC) and
incongruent (CAF/4HBA) cocrystal pairs were selected. For the first time
generation of anhydrous phase of CAF: 4HBA cocrystal in 1:1 stoichiometric
ration was reported and generation of metastable cocrystal phase of CA
CBZ: SAC form II was reported.
The application of this technology was explored in generating phase
pure metastable polymorph of paracetamol which retain higher
compressibility and dissolution rate. The potential of MASCW micronisation
process, theophylline is used as the model component to produce micro sized particles for pulmonary drug delivery system via dry powder inhaler
(Foradil inhaler). The results demonstrate that the THF particles generated
using MASCW process displayed greater aerodynamic performance
compared to conventional spray-dried THF sample.
In the final chapter, synthesis of inorganic biomaterial (nano crystalline hydroxyapatite) was reported for the first time and the prospects of
combining API like ibuprofen (IBU) with a biologically active component like
nano-crystalline hydroxyapatite (HA) through hydrogen bonding was
mechanistically explained using X-ray diffractometer and spectroscopic
techniques.
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/18177 |
| Date | January 2018 |
| Creators | Jadav, Niten B. |
| Contributors | Paradkar, Anant R, Vangala, Venu R. |
| Publisher | University of Bradford, School of Life Sciences |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Thesis, doctoral, PhD |
| Rights | <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/"><img alt="Creative Commons License" style="border-width:0" src="http://i.creativecommons.org/l/by-nc-nd/3.0/88x31.png" /></a><br />The University of Bradford theses are licenced under a <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/">Creative Commons Licence</a>. |
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