Development and mechanical characterization of bioadhesive semi-solid, polymeric systems containing tetracycline for the treatment of periodontal diseases.
OBJECTIVE
This study examined the mechanical characteristics and release of tetracycline from bioadhesive, semi-solid systems which were designed for the treatment of periodontal diseases.


METHODS
Tetracycline release into phosphate buffered saline (pH 6.8, 0.03 M) was examined using a Caleva 7ST dissolution apparatus at 37 degrees C. The mechanical properties of each formulation (hardness, compressibility, adhesiveness, elasticity and cohesiveness) were determined using texture profile analysis. Syringeability was measured using the texture analyser in compression mode as the work of syringeability i.e. the force required to express the product from a periodontal syringe over a defined distance.


RESULTS
Tetracycline release from all formulations was zero-order for 24-54 h and ranged from 1.59 +/- 0.20 to 15.80 +/- 0.50 mg h-1. Increased concentrations of hydroxyethylcellulose (HEC) decreased the rate of release of tetracycline, due to the concomitant increase in product viscosity and the subsequent decreased rate of penetration of dissolution fluid into the formulation. Conversely, an increased polyvinylpyrrolidone (PVP) concentration increased tetracycline release rates, due to an increased formulation porosity following dissolution of this polymer. Increased concentrations of HEC and PVP increased the hardness, compressibility and work of syringeability of the semi-solid formulations, due to increased product viscosity. An increase in formulation adhesiveness, a parameter related to bioadhesion, was observed as the concentrations of HEC and PVP were increased, illustrating the adhesive nature of these polymers. Increased concentrations of HEC and PVP enhanced the semi-solid nature of the product, resulting in decreased product elasticity and cohesiveness. Several statistically significant interactions between polymeric formulation components were observed within the factorial design, with respect to rate of release and all mechanical properties. These interactions arose because of variations in the physical states (dissolved or dispersed) of polymeric formulation components.


CONCLUSIONS
The optimal choice of bioadhesive formulation for use in periodontal disease will involve a compromise between achieving the necessary release rate of tetracycline and the mechanical characteristics of the formulation, as these factors will affect clinical efficacy and the ease of product application into the periodontal pocket.
Jones
D S
DS
School of Pharmacy, Queen's University of Belfast, Northern Ireland, United Kingdom.
Woolfson
A D
AD
Djokic
J
J
Coulter
W A
WA
D000180:Acrylic Resins / Q000008:administration & dosage / Q000737:chemistry; D000269:Adhesives / Q000008:administration & dosage / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry; D002482:Cellulose / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D004333:Drug Administration Routes; D006801:Humans; D010510:Periodontal Diseases / Q000188:drug therapy*; D010514:Periodontal Pocket; D010592:Pharmaceutic Aids / Q000008:administration & dosage / Q000737:chemistry; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry*; D011205:Povidone / Q000008:administration & dosage / Q000737:chemistry; D013752:Tetracycline / Q000008:administration & dosage* / Q000737:chemistry
D000180:Acrylic Resins; D000269:Adhesives; D000900:Anti-Bacterial Agents; D010592:Pharmaceutic Aids; D011108:Polymers; C030312:calcium polycarbophil; D002482:Cellulose; C002283:hydroxyethylcellulose; D013752:Tetracycline; D011205:Povidone