Micromatricial metronidazole benzoate film as a local mucoadhesive delivery system for treatment of periodontal diseases.
The main objective of this study was to develop a local, oral mucoadhesive metronidazole benzoate (MET) delivery system that can be applied and removed by the patient for the treatment of periodontal diseases. Mucoadhesive micromatricial chitosan/poly(epsilon-caprolactone) (CH/PCL) films and chitosan films were prepared. Thermal behavior, morphology, and particle size measurements were used to evaluate the prepared films. The effect of different molar masses of CH and different ratios of medium Mwt molar mass chitosan (MCH):PCL on water absorption, in vitro bioadhesion, mechanical properties, and in vitro drug release was examined. In vivo performance of the selected formulation was also evaluated. Differential scanning calorimetry examination revealed that MET existed mainly in amorphous form. Under microscopic examination, PCL microparticles were homogeneously dispersed in the films. The use of different molar masses of CH and different ratios of (MCH):PCL affected the size of the entrapped particles. Addition of PCL significantly decreased percentage water uptake and bioadhesion force compared with pure CH film. With regard to mechanical properties, the 2-layered film containing 1:0.625 MCH:PCL had the best tensile properties. At fixed CH:PCL ratio (1:1.25), the slowest drug release was obtained from films containing high molar mass CH. On the other hand, the 2-layered film that consisted of 1:0.625 MCH:PCL had the slowest MET release. In vivo evaluation of the selected film revealed that metronidazole concentration in saliva over 6 hours ranged from 5 to 15 microg/mL, which was within and higher than the reported range of minimum inhibitory concentration for metronidazole. A significant in vitro/in vivo correlation under the adopted experimental conditions was obtained.
El-Kamel
Amal Hassan
AH
Department of Pharmaceutics, Faculty of Pharmacy, King Saud University, PO Box 22452, Riyadh 11495, Kingdom of Saudi Arabia. amalelkamel@yahoo.com
Ashri
Lubna Y
LY
Alsarra
Ibrahim A
IA
D000268:Adhesiveness; D000890:Anti-Infective Agents / Q000008:administration & dosage*; D048271:Chitosan / Q000008:administration & dosage; D003692:Delayed-Action Preparations; D006801:Humans; D008795:Metronidazole / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008970:Molecular Weight; D009061:Mouth Mucosa / Q000378:metabolism*; D010316:Particle Size; D010510:Periodontal Diseases / Q000188:drug therapy*; D011091:Polyesters / Q000008:administration & dosage; D012463:Saliva / Q000378:metabolism; D012995:Solubility; D017155:Wettability
D000890:Anti-Infective Agents; D003692:Delayed-Action Preparations; D011091:Polyesters; D008795:Metronidazole; C016240:polycaprolactone; D048271:Chitosan