Preparation and evaluation of doxycycline hydrochloride and bromhexine hydrochloride dosage forms for pigeons
Objective: To prepare and evaluate three different dosage forms, containing doxycycline hydrochloride (HCI) and bromhexine hydrochloride (HCI) respectively and in combination, for the treatment of respiratory diseases in pigeons. Background: Birds have held a place in man's affection since the ancient Egyptians and Romans kept birds. Europeans have successfully bred birds, especially smaller birds and pigeons, for centuries. Only in recent years, however, have science and medicine been applied to aviculture and pet care. Pigeon racing is one of the sports not well known to the general public. These sportsmen invest a great deal to ensure that their pigeons are disease free. During racing they are exposed to infectious agents in the racing baskets and bring these pathogens back to the racing flock. If you ask any experienced flier what health problem he fears most for his pigeons during the racing season, he will probably say respiratory infection. Respiratory diseases are very common in pigeons. They are the major cause of poor performance and pigeon loss during the racing season. Doxycyline HCI, a broad-spectrum antibiotic, is the world-wide veterinary therapeutic agent of choice for the treatment of Chlamydia, a principle cause of respiratory infection. Doxycyline HCI has several advantages: greater activity, providing effective blood levels for up to 20 hours after a single dose compared to 4 hours for older tetracyclines; causes less disruption to the normal bowel bacteria; has less detrimental effect on the immune system; and is less affected by calcium and other minerals. Bromhexine HCI is an expectorant drug, promoting bronchial secretion and having mucolytic properties. It is commonly used in combination with antibiotics such as doxycycline HCI for the treatment of respiratory infections in the pigeon loft. Because avian medicine has not been commercialised as much as those for human use, it has left fanciers experimenting with dosage forms and strengths resulting in severe consequences. There is a great need for sophisticated medication developed specifically for the pigeon market. Methods: This study investigated the formulation of a direct compressed tablet and a water-soluble powder containing doxycycline HCI and bromhexine HCI respectively and in combination. The formulation and evaluation of the stability of an ophthalmic solution, containing doxycycline HCI was also investigated. Initial test were done on all three formulations. The tablets were inspected visually and tested for uniformity of mass, hardness, friability, disintegration, assay and dissolution. The water-soluble powder was tested for its pH, constitution time, assay, moisture content and visual properties. An "in use" assay was also done on the doxycycline HCI powder. Three containers (stainless steel, glass and plastic) were used and the powder was dissolved in tap water (5 mglml). Samples were taken from every container after 0, 6, 12 and 24 hours and analysed. The results obtained were compared to the same powder but with no citric acid in the formulation. The same containers and time intervals were used for the comparing powder. The ophthalmic solution's appearance, pH, density, viscosity, assay, particulate matter and preservative efficacy were tested. The formulations were stored at three different temperatures and humidities for three months. The above mentioned tests were repeated after every month. An HPLC method for the simultaneous determination of doxycycline HCI and bromhexine HCI was developed and validated. Results and discussion: Based on the different test results generated over the twelve weeks of stability evaluation of the products that were developed in this study, doxycycline HCI and bromhexine HCI, respectively and in combination, seemed to have been relatively stable. The final tablets, water-soluble powders and ophthalmic solution formulations remained stable. The "in use" assay of the powder containing citric acid showed no discoloration, precipitation or breakdown when dissolved in water for a period of 24 hours. The powder lacking the citric acid showed discoloration after only 3 hours. This powder showed significant breakdown as well. The containers used for the storage of the tablets and the powders didn't seal tight enough. The moisture uptake was very high resulting in poor disintegration and dissolution times. Therefore the powder and the tablets should be stored in tightly sealed containers with enough silica as drying agent. The containers used for the tablets, powders and ophthalmic solution respectively, seemed not to influence the stability of the formulations negatively. The newly developed and validated HPLC method was used to analyse the stability samples and it proved to be reliable and easy to execute. Conclusion: Accelerated stability tests indicated that the formulations remained stable and that no significant breakdown occurred. Complete stability trial studies should however be conducted to claim their stability. The newly developed HPLC method was used over the twelve-week period to analyse accelerated stability samples, and it proved to be reliable and easy to carry out.
- ETD@PUK