Synergistic Pulmonary Delivery via Cocrystal Based Dry Powder Inhaler: Theophylline and Glycopyrronium Bromide Combination
Harita Desai, Sakshi Jaiswal, Gaurav Bhave
Abstract:
Theophylline is widely used for Chronic Obstructive Pulmonary Disease and asthma as a bronchodilator drug. Glycopyrronium bromide (GB) is a bronchodilator belonging to the class of Muscarinic antagonists. Theophylline drug has been widely studied for phase transformation and crystal structure properties. The objective of the current research work was to develop drug-drug cocrystals comprising of Theophylline and Glycopyrronium bromide by sonocrystallization method in stoichiometric ratios of 1:1, 1:2 and 2:1. The cocrystals were evaluated for visual morphology, saturated solubility, in vitro drug release, infrared spectroscopy, differential scanning calorimetry, x-ray diffraction studies, and scanning electron microscopy. Cocrystals with highest saturation solubility were considered optimised and were further freeze-dried with a carrier and formulated into dry powder inhaler. The freeze-dried cocrystals were evaluated for flow properties, FTIR, XRD, DSC, SEM studies and in vitro lung deposition studies. Based on solubility and dissolution rate, 1:1 was found to be the most optimized stoichiometric ratio. The Theophylline: Glycopyrronium cocrystal in the ratio of 1:1 was found to show 8 fold enhancement in saturated solubility in water and 8.6 fold enhancement in saturated solubility in simulated lung fluid pH 7.4. FTIR, DSC and XRD studies were found to confirm successful cocrystallization by sonocrystallization. The freeze-dried cocrystals of Theophylline and Glycopyyronium bromide in ratio of 1:1 were found to exhibit fair flow properties. After nebulization, around 98.24% of the drug was deposited in stages 1-7 of Anderson Cascade Impactor, where it was found to be within the respirable range.
Keywords: Theophylline, Glycopyrronium Bromide, Sonocrystallization, Asthma, Bronchodilator, Drug-Drug Cocrystal.
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