Subcutaneous implants preparations

Naltrexone in combination with lactide/glycolide copolymer has been investigated (83-87). Chiang (85) reported the clinical evaluations of a bead preparation containing 70% naltrexone and 30% of a 90 10 lactide/glycolide copolymer. Each subject received a 10-mg i.v. dose of naltrexone and a 63-mg dose by subcutaneous implantation of the beads. Average plasma naltrexone levels were maintained at 0.3-0.4 ng/ml for approximately 1 month. Two out of three subjects experienced a local inflammatory reaction at the site of implantation. This unexplained problem prevented further clinical testing of... 

The present study investigates a biodegradable polymer, poly(DL-lactic acid) (DL-PLA), as the microcapsule wall. Tablets of microcapsules prepared with this method should be capable of use as subcutaneous implants. Three different compression forces, 2, 5 and 10 kN, were used, with core wall ratios of 1 1 and 2 1. For comparison, the same proportions of drug and coating polymer were compressed without prior microencapsulation. 

Only one implantable contraceptive preparation is available at present in the USA. Etonogestrel, also used in some oral contraceptives, is available in the subcutaneous implant form listed in Table 40-3. Several hormonal contraceptives are available as vaginal rings or intrauterine devices. Intramuscular injection of large doses of medroxyprogesterone also provides contraception of long duration. 

Gupta G, Saxena BB, Landesman R, Ledger WJ. Preparation, properties, and release rate of norethindrone (NET) from subcutaneous implants. In Zatuchni GI, Goldsmith A, Shelton JD, Seiarra JJ, editors. Long-Acting... 

Some limitations are that the amount of drug that can be injected in this fashion is fairly small and that the injected drug must not irritate or inflame the subcutaneous tissues. The subcutaneous route can also be used when certain types of drug preparations are implanted surgically beneath the skin, so that the drug is slowly dispersed from the implanted preparation and then absorbed into the bloodstream for prolonged periods of time.62,86 A common example of this form of subcutaneous administration is the use of implanted hormonal contraceptive products (e.g., Norplant).9,53 The use of these implantable contraceptives is discussed in more detail in Chapter 30. 

Block terpolymers prepared by Cheng [5] consisting of poly(A-isopropyl acrylamide-b-polyethyleneoxide-b-A-isopropyl acrylamide), (II), were effective as thermally reversible gels and used as subcutaneous implants, joint or tissue spacers, and biological filler for wrinkles or cosmetic implants. Methacrylamide analogues were prepared by Gutowska [6]. 

The method used for preparation of the PHEMA hydrogels was described in an earlier report (33). Fully hydrated samples equilibrated at room temperature were immersed in Millipore water at 37 0.5 °C for at least 2 weeks before calcification experiments commenced. The incorporation of citric acid into PHEMA was performed by the swelling equilibrium partition method using a 2.5 M citric acid solution. Prior to incubation in SBF or subcutaneous implantation of the hydrogels in rats, the citric acid-equilibrated gels were kept in Millipore water at 37 0.5 °C for one week. The hydrogels were sterilized by autoclaving for 20 min before implantation in the rats. 

Yamamoto, L, Maruyama, H., Takahashi, M., and Komiyama, K. (1986). The effect of dietary or intraperitoneally injected seaweed preparations on the growth of sarcoma-180 cells subcutaneously implanted into mice. Cancer Lett. 30(2), 125-131. 

Ertefai, S., Gough, D. A. (1989). Physiological preparation for studying the response of subcutaneously implanted glucose and oxygen sensors (Translated from Enghsh). Journal of Biomedical Engineering, 11(5), 362-368 (in eng). 

A ketene acetal-terminated prepolymer was first prepared from 2 eq of the diketene acetal 3,9-bis(ethylidene-2,4,8,10-tetraoxaspiro-[5,5]undecane) and 1 eq of the diol 3-raethyl-l,5-pentanediol and. then 30 wt% levonorgestrel, 7 wt% Mg(OH)2j and a 30 mole% excess of 1,2,6-hexanetriol mixed into the prepolymer. This mixture was then extruded into rods and cured. Erosion and drug release from these devices was studied by implanting the rod-shaped devices subcutaneously into rabbits, explanting at various time intervals, and measuring weight loss and residual drug (15). 

FIGURE 18 In vivo cumulative weight loss (o) and cumulative release of levonorgestrel (o) from a crossUnked polymer prepared from a 3,9-bis(ethylidene-2,4,8,10-tetraoxaspiro[5,5]undecane)/3-methyl-1,5-pentanediol prepolymer crossUnked with 1,2,6-hexane triol. Polymer rods, 2.4 X 20 mm, containing 30 wt% levonorgestrel and 7.1 mol% Mg(OH)2. Devices implanted subcutaneously in rabbits. (From Ref. 15.)... 

Some subcutaneous and intrauterine implants of progesterone have also been used which are prepared in biodegradable polymeric matrices. 

Solid-type sarcoma 180 was prepared by subcutaneous transplantation into the right abdomen of mice on day 0. The indicated amounts of ergosterol were administered orally for 20 consecutive days, starting 12 h after the implantation of tumor cells. 

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