Investigation of injection moulding for novel drug delivery systems. An investigation into the use of injection moulding to produce pharmaceutical dosage forms and to understand the relationship between materials, processing conditions and performance, in particular drug release and stability

The feasibility of the injection moulding (IM) was explored for the development of novel drug delivery systems. Controlled release formulations were developed using a substituted cellulose derivative, hydroxypropyl methyl cellulose acetate succinate (HPMCAS) and a graft co-polymer (Soluplus®). BCS class II drugs ibuprofen and the felodipine were selected based on their physicochemical properties. In the present work, a homogenous dispersion of drugs in the polymer matrices was achieved using Hot Melt Extrusion (HME) and extruded pellets obtained were used for the development of the injection moulded systems. Four systems were developed using the IM consisting of ibuprofen-HPMCAS, ibuprofen-Soluplus®, felodipine-PEO-HPMCAS and felodipine-Soluplus®. The ibuprofen acts as a good plasticiser compared to felodipine therefore, felodipine containing IM systems required a plasticiser (PEO) when processed with HPMCAS. The analysis of extruded pellets and injection moulded systems using modulated DSC (MDSC) and Raman spectroscopy confirmed the formation of an amorphous molecular dispersion (i.e solid solution) in the case of all four systems. The phase separation behaviour and the amorphous stability of the systems was studied at various stress conditions. This revealed the “surface crystallisation” behaviour of the ibuprofen-HPMCAS systems. Temperature-composition phase diagram constructed based on the melting point depression and the Flory-Huggins lattice solution theory provided the explanation for the phase separation and crystallisation behaviour of ibuprofen-HPMCAS systems. The advanced characterisation techniques like DMA, 2D XRD and 3D laser microscopy provided the detailed understanding of crystal habits, phase seperation and surface crystallisation. The significant effect of the stress conditions on the rate of shrinkage was observed where, higher shrinkage tendency of a HPMCAS IM system was observed compared to Soluplus® IM systems. The extruded pellets provided the faster drug release compared to the moulded tablets suggests the effect of particle size as well as the densification during IM on the dissolution rate of the dosage form. The nature of the polymer and processing history were the contributing factors for the dissolution of the dosage forms.The thesis is hardbound in two volumes. Volume II starts at Chapter 5, page 135

Study of the clinical profile and treatment outcome of pulmonary and extrapulmonary tuberculosis patients coming to respiratory medicine OPD

Background: The major risk factors for development of tuberculosis are extremes of age, malnutrition, overcrowding and immune deficient states like AIDS, diabetes mellitus, measles, whooping cough and leukaemia. Chronic malaria and worm infestation are less important risk factors. Tobacco smoking, high alcohol consumption, corticosteroid therapy and immunosuppressive drug therapy reduce body defences there by increasing the susceptibility to tuberculous infection. This study was undertaken to analyse the various clinical presentations in patients with pulmonary tuberculosis and extra pulmonary tuberculosis. Methods: This was a retrospective study of patients from October 2020 to September 2022 (2 years). Data collected from 300 patients who were diagnosed with pulmonary and extrapulmonary tuberculosis visited. The subjects were divided into subjects who had pulmonary TB (PTB), and who had extrapulmonary TB (EPTB). Results: The most common systemic disorders accompanying EPTB were DM (n=11; 8.8%) and chronic renal failure (n=8; 6.4%); while DM (n=16; 9.1%) and chronic obstructive pulmonary disease (n=13; 7.4%) were those detected frequently in PTB group. Conclusions: Present study showed higher percentage of males and greater predominance of pulmonary TB. It is also observed high percentage extrapulmonary TB. High percentage of positive treatment outcomes with fewer relapses and failures was observed in this study. A high positive treatment outcome noted may be attributed to the availability of specialist doctors and diagnostic facilities in the tertiary care centre

Prevalence of obstructive airway disease in pulmonary function tests of patients visiting respiratory medicine out patient department

Background: The recognition of obstructive airway disease as a public health problem, however, has failed to keep pace with its increasing impact on health-care resources. This study is conducted to evaluate the prevalence of obstructive airway disease in pulmonary function tests (PFT) of patients visiting respiratory medicine out patient department (OPD). Methods: This is a retrospective study of patients from October 2020 to September 2022 (2 years), on 80 subjects reporting to respiratory medicine OPD, MGM medical college, Aurangabad. Data collected from 80 subjects who were diagnosed with obstructive airway disease in PFT. Results: The study population had a COPD prevalence of 16 (19.7%). GOLD criterion revealed that 54.2% (9/16) of COPD patients had mild COPD. This research showed no evidence of very severe COPD. In terms of gender distribution, 8 (16.6%) of 46 males and 7 (19.5%) of 34 women had COPD. However, there was no statistically significant (p=0.167) difference in COPD prevalence between sexes. Furthermore, univariable analysis revealed no significant differences in marital status (p=0.836), co-morbidities (p=0.541), family size (p=0.535), educational status (p=0.827), employment status (p=0.643), and medical visits (p=0.366) between persons with and without COPD. Conclusions: According to the findings of this research, the variables that increase a person's likelihood of developing COPD are as follows: advancing age, prolonged exposure to smoke from biomass burning, tobacco use, and inadequate ventilation in the kitchen

Study of the bronchoscopic evaluation of patients undergoing bronchoscopy in respiratory medicine department

Background: Bronchoalveolar lavage or BAL is a minimally invasive procedure that involves instillation of sterile normal saline into a subsegment of the lung, followed by suction and collection of the instillation for analysis. This procedure is typically facilitated by the introduction of a flexible bronchoscope into a sub-segment of the lung. The purpose of this study was to investigate the pathological variations in the tracheobronchial tree in various respiratory diseases. Methods: The study evaluated the bronchoscopic profile of 150 patients who underwent flexible bronchoscopy in the respiratory medicine department of MGM Medical College in Aurangabad, India from October 2020 to September 2022. Results: The majority of the patients were males (65%) and above the age of 50. The most common reason for bronchoscopy was radiological opacity (80% of cases), followed by diffuse pulmonary infiltration (10%). The study found that bronchoscopy was useful in obtaining samples for diagnosis of various respiratory diseases, including malignancies, tuberculosis, bacterial pneumonia, and hematological malignancies. The study also noted the therapeutic utility of bronchoscopy in managing inoperable stenosis of the central airways. Conclusions: The authors concluded that bronchoscopy is an important diagnostic and therapeutic tool for the management of pulmonary diseases

Injection moulded controlled release amorphous solid dispersions: Synchronized drug and polymer release for robust performance

YesA study has been carried out to investigate controlled release performance of caplet shaped injection moulded (IM) amorphous solid dispersion (ASD) tablets based on the model drug AZD0837 and polyethylene oxide (PEO). The physical/chemical storage stability and release robustness of the IM tablets were characterized and compared to that of conventional extended release (ER) hydrophilic matrix tablets of the same raw materials and compositions manufactured via direct compression (DC). To gain an improved understanding of the release mechanisms, the dissolution of both the polymer and the drug were studied. Under conditions where the amount of dissolution media was limited, the controlled release ASD IM tablets demonstrated complete and synchronized release of both PEO and AZD0837 whereas the release of AZD0837 was found to be slower and incomplete from conventional direct compressed ER hydrophilic matrix tablets. Results clearly indicated that AZD0837 remained amorphous throughout the dissolution process and was maintained in a supersaturated state and hence kept stable with the aid of the polymeric carrier when released in a synchronized manner. In addition, it was found that the IM tablets were robust to variation in hydrodynamics of the environment and PEO molecular weight.The research was funded by AstraZeneca, Sweden