hydroxyethylcellulose and Periodontal-Diseases

This study describes the formulation, characterisation and preliminary clinical evaluation of mucoadhesive, semi-solid formulations containing hydroxyethylcellulose (HEC, 1-5%, w/w), polyvinylpyrrolidine (PVP, 2 or 3%, w/w), polycarbophil (PC, 1 or 3%, w/w) and tetracycline (5%, w/w, as the hydrochloride). Each formulation was characterised in terms of drug release, hardness, compressibility, adhesiveness (using a texture analyser in texture profile analysis mode), syringeability (using a texture analyser in compression mode) and adhesion to a mucin disc (measured as a detachment force using the texture analyser in tensile mode). The release exponent for the formulations ranged from 0.78+/-0.02 to 1. 27+/-0.07, indicating that drug release was non-diffusion controlled. Increasing the concentrations of each polymeric component significantly increased the time required for 10 and 30% release of the original mass of tetracycline, due to both increased viscosity and, additionally, the unique swelling properties of the formulations. Increasing concentrations of each polymeric component also increased the hardness, compressibility, adhesiveness, syringeability and mucoadhesion of the formulations. The effects on product hardness, compressibility and syringeability may be due to increased product viscosity and, hence, increased resistance to compression. Similarly, the effects of these polymers on adhesiveness/mucoadhesion highlight their mucoadhesive nature and, importantly, the effects of polymer state (particularly PC) on these properties. Thus, in formulations where the neutralisation of PC was maximally suppressed, adhesiveness and mucoadhesion were also maximal. Interestingly, statistical interactions were primarily observed between the effects of HEC and PC on drug release, mechanical and mucoadhesive properties. These were explained by the effects of HEC on the physical state of PC, namely swollen or unswollen. In the preliminary clinical evaluation, a formulation was selected that offered an appropriate balance of the above physical properties and contained 3% HEC, 3% PVP and 1% PC, in addition to tetracycline 5% (as the hydrochloride). The clinical efficacy of this (test) formulation was compared to an identical tetracycline-devoid (control) formulation in nine periodontal pockets (>/=5 mm depth). One week following administration of the test formulation, there was a significant improvement in periodontal health as identified by reduced numbers of sub-

Topics: Acrylic Resins; Algorithms; Anti-Bacterial Agents; Cellulose; Chemistry, Pharmaceutical; Drug Carriers; Excipients; Gels; Humans; Mouth Mucosa; Periodontal Diseases; Povidone; Syringes; Tetracycline; Tissue Adhesives

To design a suitable periodontal disease formulation using basic fibroblast growth factor (bFGF), legally available thickeners were evaluated focusing on their viscosity, extrusive force from a syringe, flow property and inertness to bFGF. Thirteen candidate thickeners showed appropriate viscosity (about 1×10⁴ mPa·s), and further evaluations were conducted on them. Flow property was evaluated by the tilting test tube method. As a result, most thickener solutions with the optimum viscosity showed appropriate flow time (about 100 s) and the flow time did not depend on thickener concentration, whereas the extrusive force from a syringe depended on thickener concentration despite the thickener type and grade. Thickener solutions of 2-3% showed ideal result (10-20 N) and thickener solutions prepared outside of the concentration range (2-3%) were found to show unsuitable extrusive force. Consequently, to obtain required properties for a dental drug formulation, thickener solutions needed to show adequate viscosity (about 1×10⁴ mPa·s) at 2-3% thickener concentration. In addition, several types of cellulose derivatives showed inertness to the bFGF because of their structure, without strong ionic dissociable groups, and neutral pH. Overall, the present work demonstrates that some water-soluble cellulose derivatives, such as hydroxypropylcellulose (HPC) and hydroxyethylcellulose (HEC), were suggested to have required properties for a dental drug formulation including bFGF.

Topics: Cellulose; Chemistry, Pharmaceutical; Excipients; Fibroblast Growth Factor 2; Humans; Periodontal Diseases; Recombinant Proteins; Viscosity

Mucoadhesive tablets using different mixture of cellulose and polyacrylic derivatives were prepared in order to obtain new formulations containing metronidazole for periodontal disease treatment. All tablets were characterized by swelling studies, ex vivo and in vivo mucoadhesive time, ex vivo mucoadhesion force, in vitro and in vivo release. The best mucoadhesive performance and the best in vitro drug release profile were achieved by using hydroxyethyl cellulose (HEC) and carbomer 940 2:2 ratio. The chosen tablet, containing 20 mg of metronidazole, performed 12 h drug sustained release with buccal concentrations always higher than its MIC.

Topics: Acrylic Resins; Adhesives; Animals; Cellulose; Chemistry, Pharmaceutical; Drug Delivery Systems; Drug Evaluation, Preclinical; Humans; Metronidazole; Mouth Mucosa; Periodontal Diseases; Saliva; Swine; Tablets; Time Factors; Water

There is increasing evidence that cells of the epithelial root sheath synthesize enamel matrix proteins and that these proteins play a fundamental role in the formation of acellular cementum, the key tissue in the development of a functional periodontium. The purpose of the present study was to explore the effect of locally applied enamel matrix and different protein fractions of the matrix on periodontal regeneration in a buccal dehiscence model in monkeys. Buccal, mucoperiosteal flaps were raised from the canine to the 1st molar on each side of the maxilla. The buccal alveolar bone plate, the exposed periodontal ligament and cementum were removed. Various preparations of porcine enamel matrix with or without vehicles were applied before the flaps were repositioned and sutured. After 8 weeks, the healing was evaluated in the light microscope, and morphometric comparisons were made. Application of homogenized enamel matrix or an acidic extract of the matrix containing the hydrophobic, low molecular weight proteins, amelogenins, resulted in an almost complete regeneration of acellular cementum, firmly attached to the dentin and with collagenous fibers extending over to newly formed alveolar bone. After application of fractions obtained by neutral EDTA extraction containing the acidic, high molecular weight proteins of the enamel matrix, very little new cementum was formed and hardly any new bone. The results of the controls in which no test substance was applied before the repositioning of the flap, were very similar to those obtained with the EDTA extracted material. Propylene glycol alginate (PGA), hydroxyethyl cellulose and dextran were tried as vehicles for the enamel matrix preparations. Only PGA in combination with the amelogenin fraction resulted in significant regeneration of the periodontal tissues.

Topics: Alginates; Alveolar Bone Loss; Alveolar Process; Amelogenin; Animals; Cellulose; Collagen; Dental Cementum; Dental Enamel Proteins; Dentin; Dextrans; Disease Models, Animal; Epithelium; Macaca fascicularis; Molecular Weight; Osteogenesis; Periodontal Attachment Loss; Periodontal Diseases; Periodontium; Pharmaceutical Vehicles; Regeneration; Surgical Flaps; Swine; Tissue Extracts; Tooth Root

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

Topics: Acrylic Resins; Adhesives; Anti-Bacterial Agents; Cellulose; Chemical Phenomena; Chemistry, Pharmaceutical; Chemistry, Physical; Drug Administration Routes; Humans; Periodontal Diseases; Periodontal Pocket; Pharmaceutic Aids; Polymers; Povidone; Tetracycline