Evaluation of mechanical and mucoadhesive properties of clomiphene citrate gel formulations containing carbomers and their thiolated derivatives.
The aim of our study was to prepare clomiphene citrate gel formulations that possess appropriate mechanical properties, stay on the vaginal mucosa for a long period of time, and provide sustained drug release for the local treatment of human papilloma virus infections. In this respect, 1% CLM gels including polyacrylic acid (PAA) polymers such as Carbopol 934P (C934P), Carbopol 971P (C971P), Carbopol 974P (C974P) in various concentrations, and their conjugates containing thiol groups were prepared. Polyacrylic acid-cysteine (PAA-Cys) conjugates were synthesized in laboratory conditions. Mechanical properties of the gels such as hardness, compressibility, elasticity, adhesiveness, and cohesiveness were measured by TA-XTPlus texture analyzer and the vaginal mucoadhesion of formulations was investigated by mucoadhesion test. Based on obtained data, gel formulations containing C934P and its conjugate had appropriate hardness and compressibility to be applied to the vaginal mucosa and highest elasticity to show good spreadability and highest cohesion to prevent the disintegration of gel in the vagina. The mucoadhesion of the gels changed significantly depending on the polymer type and concentration (p < 0.05). The addition of conjugates containing thiol groups caused an increase in mucoadhesion (p < 0.05). The gels containing C934P-Cys showed highest adhesiveness and mucoadhesion due to the highest amount of thiol groups. A significant decrease was observed in the drug release of gel formulations as the polymer concentration increased (p < 0.05). The increase in the drug release related to the conjugate addition was not statistically significant (p > 0.05). A change in the amount of CLM was not observed in all formulations at the end of the stability test.
Cevher
Erdal
E
Faculty of Pharmacy, Department of Pharmaceutical Technology, Istanbul University, Istanbul, Turkey. ecevher@istanbul.edu.tr
Taha
M A M
MA
Orlu
M
M
Araman
A
A
D000179:Acrylates / Q000737:chemistry*; D000268:Adhesiveness; D000282:Administration, Intravaginal; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D002417:Cattle; D002626:Chemistry, Pharmaceutical; D002996:Clomiphene / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D019245:Compressive Strength; D003545:Cysteine / Q000031:analogs & derivatives / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D004548:Elasticity; D005260:Female; D005782:Gels; D006244:Hardness; D006801:Humans; D007700:Kinetics; D009093:Mucus / Q000378:metabolism; D030361:Papillomavirus Infections / Q000188:drug therapy; D012995:Solubility; D014621:Vagina / Q000378:metabolism
D000179:Acrylates; D000998:Antiviral Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005782:Gels; C492577:carbopol 971P; C117167:carbopol 974P NF; D002996:Clomiphene; C453622:carbopol 934P; D003545:Cysteine