Polymer materials for biomedical use obtained by radiation methods. IV. the therapeutic system for local release of prostaglandins
Rosiak, J.; Olejniczak, J.
Polimery W Medycynie 19(3-4): 93-106
1989
ISSN/ISBN: 0370-0747 PMID: 2641404 Document Number: 326780
N-Vinylpyrrolidone was used in glass vials for polymerization, and the therapeutical system was secured by means of 30-35 mm long columns of 8.5 mm diameter that ended in a tip of 12 mm diameter of one side. Inserts were placed into an external solution and fastened by silk threads that served the potential future purpose of removal from the neck of the uterus during the medically-indicated term of use. Cobalt-60, Polish-made BK-10,000 cobalt bombs, and Canadian-made Gammacell were placed in the irradiation chamber to provide irradiation. Prostaglandin F2-alpha (PGF2-alpha) (Enzaprost made in Hungary) was used as active substance. The preparation contained 5 mg PGF2-alpha and 40.8 mg of sodium octanate in 1 ml of aqueous solution. The degree of PGF2-alpha release from the inserts was demonstrated by spectrophotometry. The 3-phase process included polymerization of N-vinylpyrrolidone by irradiation and the network of derived polymers; the introduction of prostaglandins into the inserts that were formed; and sterilization irradiation. After the irradiation of the matrix by doses greater than 4.5 kGy (kilo Gray) the presence of monomers could not be determined by spectrophotometry. Nonsoluble forms appeared in the matrix only under a dose exceeding 10 kGy: gel (consisting of a spatial network of polyvinylpyrrolidone (PVP) chains) swelled in the solution without being dissolved. The proportion of sol and gel made up 1. Under 30 kGy dose the rapidity of nonsoluble fraction formation decreased significantly, thus further irradiation was ineffective. The PVP matrix obtained by irradiating the system with a 25 kGy dose contained about 70% nonsoluble fraction and about 30% sol. This meant that after 24 hours of extraction about 30% of the matrix was precipitated. The content of nonsoluble fraction increased for over 10 seconds during the 1st minute, and then stabilized at around 80%. A similar 10% increase of gel content could be obtained by an additional 15 kGy dose, but this would only prolong the process and add to the cost of producing inserts of a particular shape and size whose gel content fraction formation required about 30 minutes. Heating of the PvP inserts at 383 degrees Kelvin (K) after 25 kGy irradiation yielded a degree of 25 of equilibrium swelling (absorption of 25 times more water than their mass). It is sufficient to place the inserts in a 1 ml solution of PGF2-alpha solution for 1 hour in order to introduce 5 mg of it into them; but for deeper penetration 3 hours in required. After drying the finished inserts for 15 hours, in vitro experiments showed that 85% of PGF2-alpha was released into Ringer solution at 310 K after 3 hours. The above process is detailed in a patent application.