Info

Fig. 19. Rate of release of selenium from push-melt ruminal bolus.

intestional and lung nematodes and will prevent the establishment of new infections for 135 days. Treatment with the bolus will also control established mange mites, sucking lice infections, and migrating grubs. For ticks, the bolus will interfere with the engorgement of blood and the completion of the life cycle. Thus the bolus is a highly effective product for the once per grazing treatment of the listed parasites.

This same push-melt system has been developed for the delivery of selenium to grazing cattle.76 The system is similar in design to that described above except that the capscreen is not present, different waxes are used for the formulation and the system is not prehydrated. A typical release curve showing the in vitro and in vivo release rate for selenium from this system is shown in Figure 19. Note that the steady state release rate of approximately 3 mg/day is achieved after about 20 days of delivery and that approximately the same rate per day is seen both in vivo and in vitro. This system was compared in an in vivo study against an erodible system in the form of pellets that contain approximately 10% selenium.77 The study demonstrated that the administration of two boluses, one on day 1 and one on day 120, leads to the effective delivery of this nutritional supplement for the proposed period and produced significantly higher plasma levels of selenium than was achieved with the pellets or untreated controls.

Fig. 20. Release of CP-53,607 from modified Paratect® bolus. The device contains 6 g of polyethylene oxide 600 pellets and 28 ml of a 5% solution of CP-53,607 in octyl alcohol. One membrane is sintered polyethylene; the other is impregnated with gelled cellulose triacetate and polyethylene glycol 400.78

Time (days)

Fig. 20. Release of CP-53,607 from modified Paratect® bolus. The device contains 6 g of polyethylene oxide 600 pellets and 28 ml of a 5% solution of CP-53,607 in octyl alcohol. One membrane is sintered polyethylene; the other is impregnated with gelled cellulose triacetate and polyethylene glycol 400.78

Another example of an osmotic pressure based ruminal bolus is found in the work of Thombre et al.7 Using a device similar in overall design to that of the Paratect® bolus,47'48 Thombre et al. developed a novel osmotic technology suitable for the long-term delivery of drugs wherein the drug is delivered as a solution in oil. This system utilized both the cylinder and membranes of the Paratect® bolus as described earlier, however, the membranes and core formulations were suitably modified to convert the overall mechanism of drug delivery from diffusion control to an osmotic based mechanism.

In this system the core formulation is composed of an oil such as octanol, isopropyl myristate, or soybean oil and a swellable polymer such as PEG 600 or polyvinyl alcohol dispersed as pellets within the oil. The drug is dissolved within the oil phase. As with the Paratect® bolus, one microporous polyethylene membrane is impregnated with cellulose triacetate and wetted with PEG 400. The other microporous membrane is either unimpregnated or treated with various other options to permit the membrane to be permeable to oil.

Figure 20 shows some typical in vitro release data for a system prepared from 28 ml of a 5% solution of CP-53,607 (an ionophore with potential as a growth promotent in ruminants79) containing 6 g of pelletized PEG 600. One microporous membrane disk

Fig. 21. Drug release rate versus initial drug concentration for the modified Paratect® bolus. The slope of the line is 0.34 ml/day and represents the volumetric flux of solution from the device.78

was impregnated with cellulose triacetate while the second was an unimpregnated microporous disk. Note that there is a 'burst effect' arising from release of drug initially associated with the unimpregnated disk. Following this burst, the release rate is nearly constant through >70% of the total delivery period. Figure 21 is a plot of the steady state release rate versus the initial drug concentration for a series of devices prepared with varying initial drug loads. Note the linearity of the plot. The slope of the line is 0.34 ml/day and represents the volumetric flux of fluid from the devices. This result is consistent with a mechanism where the rate of water transport across the cellulose triacetate membrane controls the overall release rate from these devices. Figure 22 provides further support for this where we see that the normalized percent drug release is independent of the nature of the oil used in the device preparation. Thus the overall rate of drug release from these devices will be dependent only upon those factors which control the water transport rate, i.e. the membrane permeability and surface area, and the activity of the swelling polymer. The described devices should have broad utility for the delivery of water insoluble/oil soluble compounds.

0 0

Post a comment