Effect of natural anionic polymers on the release rate and local concentration of metronidazole at pH near the natural gastric environment.
The aim of the study was to evaluate initially the applicability of certain natural polymers, as metronidazole binding agents in the treatment of ulcerative lesions in the gastric mucous membrane. The investigation involved systems containing metronidazole in combination with sodium alginate, citrus pectin and citrus-apple pectin. The rate of metronidazole release from the investigated preparations was evaluated after acidification to pH in gastric environment. Constant rates were determined, which were from 0.25 h-1 to 0.58 h-1 as well as half-release time, which were from 1.20 h to 2.82 h. Also, dynamic viscosity of the investigated systems was assessed--the dynamic viscosity of the gelatinous form with 2% content of sodium alginate increased by three orders of magnitude under the influence of acid pH, i.e. from about 160 cPa.s to about 30,000 cPa.s. Similarly, the viscosity of the preparation containing 4% of citrus-apple pectin increased after acidification from about 140 cPa.s to almost 40,0000 cPa.s. The use of sodium alginate and citrus-apple pectin as metronidazole carriers may prolong the time of action of the drug on pathologically changed gastric mucosa. The fraction of metronidazole which is in immediate contact with the pathologically changed surface is in concentration exceeding significantly MIC and MBC at usual oral doses.
Musiał
Witold
W
Department of Drug Form Technology, Wrocław Medical University. witold@bf.uni.wroc.pl
Kubis
Aleksander
A
D000464:Alginates / Q000494:pharmacology*; D002957:Citrus; D004337:Drug Carriers; D005750:Gastric Juice / Q000737:chemistry; D005753:Gastric Mucosa / Q000737:chemistry*; D005782:Gels / Q000737:chemistry*; D020723:Glucuronic Acid / Q000494:pharmacology*; D006603:Hexuronic Acids / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D027845:Malus; D008795:Metronidazole / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010368:Pectins / Q000494:pharmacology*; D011108:Polymers / Q000737:chemistry; D013997:Time Factors
D000464:Alginates; D004337:Drug Carriers; D005782:Gels; D006603:Hexuronic Acids; D011108:Polymers; D008795:Metronidazole; D010368:Pectins; D020723:Glucuronic Acid