Intravaginal administration of progesterone using a new technique for sustained drug release in goats

Abstract

The objective of the present study was to develop and evaluate a sustained release vaginal progesterone (P 4 ) capsule containing a mixture of mucoadhesive polymer and silicone fluid. Goats were administered a gelatin capsule containing 0.4 g of P 4 mixed in silicone fluid and either a hydroxypropylmethylcellulose (HM) or polyaclil starch (PA) base. The mean plasma P 4 concentrations at 2 and 12 h after administration were significantly higher in goats treated with PA capsules than in those with HM capsules. The plasma P 4 concentrations in goats treated with HM capsules increased and remained above 1.0 ng/ml for 96 h after administration, whereas the plasma P 4 concentrations in goats treated with PA capsules remained above 1.0 ng/ml for only 24 h after administration. In the next experiment, an HM capsule was attached to a silicone device and inserted in the vagina for 10 days. The plasma P 4 concentration remained similar to that of the natural luteal phase for 9 days. These results suggest that a mixture of mucoadhesive polymer and silicone fluid has the potential to be applied clinically as a sustained release base for estrus synchronization or hormonal therapy.

Intravaginal administration of estradiol benzoate capsule for estrus synchronization in goats

“…The EB capsule was designed to melt immediately after administration and was formulated using commercially available hard fat (Hosco S-55, Maruishi Pharmaceutical Co., Osaka) as the suppository base. The SR EB capsule was designed to melt gradually to reach a peak 24 h after administration and was formulated using an SR base developed previously in our laboratory [9].…”

“…The EB capsule was prepared by adding 1 mg of EB powder (Tokyo Chemical Industry Co., Ltd., Japan) and 0.8 ml of hard fat to a gelatin capsule (#00, volume of 1.01 ml, Matsuya Co., Osaka, Japan). For the SR capsule, 1 mg of EB powder and hard fat was placed in a small capsule (#2, volume of 0.37 ml, Matsuya Co., Osaka, Japan) and placed in the center of a large capsule (#00) filled with a SR base containing silicone fluid (Q7-9120, Dow Corning, MI, USA) as a dispersing agent and acrylic starch (SANWET®, Sanyo Chemical Co. Ltd., Kyoto, Japan) as a mucoadhesive polymer [9] (Figure 1). The capsules were then stored at 4C in a refrigerator until administration.…”

“…Goats in the PG+SR group (n = 6) were administered an SR capsule at the same time as PG treatment (day 0). The administered intravaginal EB and SR capsules were attached to a Y-shaped silicone device [9] to prevent the capsule from flowing out of the vagina. The device was removed on day 2, and by then, it was confirmed that all capsules had melted in the vagina.…”

“…Recent studies have shown that the use of mucoadhesive polymers such as polyacrylic acid bases and cellulose derivatives can improve the efficacy of drug release and absorption in the vagina [16,17]. We reported that intravaginal administration of a progesterone capsule formulated using a mixture of a mucoadhesive polymer and silicone fluid could maintain a plasma progesterone (P4) concentration similar to that in the natural luteal phase for 9 d in goats [9]. In this way, a reduction in the administration frequency using intravaginal sustained drug release can reduce the time and cost of treatment and reduce pain in animals.…”

Continuous acceleration of neural activity of the GnRH pulse generator during chronic peripheral infusion of neurokinin 3 receptor agonist in goats

“…A lower concentration of senktide may have similar effects on the GnRH pulse generator with reduced vaginal leakage. Endo et al [22] reported a sustained drug release technique using a silicon device with progesterone capsules containing a mixture of a mucoadhesive polymer and silicone fluid. To reduce the amount of senktide loss, the chronic administration of senktide using the intravaginal drug delivery system described above should be further evaluated to assess its efficacy using MUA.…”