methylcellulose and calcium-phosphate--monobasic--anhydrous

A new injectable and self-crosslinkable bone substitute (IBS2) was developed for filling bone defects. The IBS2 consisted of a chemically modified polymer solution mixed with biphasic calcium phosphate (BCP) ceramic particles. The polymer hydroxypropylmethyl cellulose was functionalized with silanol groups (Si-HPMC) and formed a viscous solution (3 wt %) in alkaline medium. With a decrease in pH, self-hardening occurred due to the formation of intermolecular -Si-O- bonds. During setting, BCP particles, 40 to 80 microm in diameter, were added to the polymer solution at a weight ratio of 50/50. The resulting injectable material was bilaterally implanted into critically sized bone defects at the distal femoral epiphyses of nine New Zealand White rabbits. The IBS2 filled the bone defects entirely and remained in place. After 8 weeks, bone had grown centripetally and progressed towards the center of the defects. Newly formed bone, ceramic, and nonmineralized tissue ratios were 24.6% +/- 5.6%, 21.6% +/- 5.8%, and 53.7% +/- 0.1%, respectively. Mineralized and mature bone was observed between and in contact with the BCP particles. The bone/ceramic apposition was 73.4% +/- 10.6%. The yield strength for the IBS2-filled defects was 16.4 +/- 7.2 MPa, significantly higher than for the host trabecular bone tissue (2.7 +/- 0.4 MPa). This study showed that BCP particles supported the bone healing process by osteoconduction while the Si-HPMC hydrogel created intergranular space for bone ingrowth. This new injectable and self-crosslinkable bone substitute could be used conveniently in orthopedic surgery for filling critical-size bone defects.

Topics: Animals; Biodegradation, Environmental; Bone Substitutes; Calcium Phosphates; Female; Femur; Hydrogels; Hypromellose Derivatives; Injections; Methylcellulose; Osseointegration; Rabbits

Synthesis of grafting silane on a hydro soluble cellulose ether (HPMC) was described. In alkaline medium, this derivate is under gel form. With a decrease of the pH, a self-hardening occurs due to the silanol condensation. For potential biomedical use, we described the silated-HPMC synthesis, the gel behavior after steam sterilization and the parameters of the silanol condensation i.e. pH, silane percentage and temperature. Minimum kinetic of the condensation was observed for pH between 5.5 and 6.5. So temperature catalyzed the reaction and the self-hardening speed was increased by silane percentage.

Topics: Animals; Bone Substitutes; Calcium Phosphates; Ceramics; Gels; Hardness; Hydrogen-Ion Concentration; Hypromellose Derivatives; Kinetics; Materials Testing; Methylcellulose; Powders; Rheology; Silanes; Sodium; Spectroscopy, Fourier Transform Infrared; Sterilization; Viscosity

A floating dosage form composed of nicardipine hydrochloride (NH) and hydroxypropylmethylcellulose acetate succinate (enteric polymer) was prepared using a twin-screw extruder. By adjusting the position of the high-pressure screw elements in the immediate vicinity of die outlet, and by controlling the barrel temperature, we were able to prepare a puffed dosage form with very small and uniform pores. It was found that the porosity and pore diameter could be controlled by the varying amount of calcium phosphate dihydrate. In the shaking test, the puffed dosage form was found to have excellent floating ability and mechanical strength in acid solution (JP First Fluid, pH 1.2). The dissolution profile of NH was controlled by the amount of wheat starch. In the dissolution test using JP Second Fluid (pH 6.8), rapid dissolution of NH and loss of buoyancy were observed. It was shown that the puffed dosage form, consisting of enteric polymer prepared using the twin-screw extruder, was very useful as a floating dosage form that was retained for a long period in the stomach.

Topics: Administration, Oral; Calcium Phosphates; Chemistry, Pharmaceutical; Dosage Forms; Kinetics; Methylcellulose; Microscopy, Electron, Scanning; Nicardipine; Vasodilator Agents

The purpose of this study was to check the chemical stability of an injectable bone substitute (IBS) composed of a 50/50 w/w mixture of 2.92% hydroxypropyl methylcellulose (HPMC) solution in deionized water containing biphasic calcium phosphate (BCP) granules (60% hydroxyapatite/40% beta-tricalcium phosphate w/w). After separation of the organic and mineral phases, capillary gas chromatography (GC) was used to study the possible modification of HPMC due to the contact with BCP granules following steam sterilisation and 32 days storage at room temperature. HPMC was extracted from IBS in aqueous medium, and a dialytic method was then used to extract calcium phosphate salts from the HPMC. The percentage of HPMC extracted from BCP was 98.5%+/-0.5%, as measured by UV. GC showed no chemical modifications after steam sterilisation and storage.

Topics: Biocompatible Materials; Calcium Phosphates; Chromatography, Gas; Hydrogen-Ion Concentration; Hypromellose Derivatives; Methylcellulose; Salts; Temperature; Time

The purpose of the study was to develop a new three-dimensional model using force, time and displacement to characterize the densification behavior of tableting materials. Normalized time (x), displacement converted to ln(1/1 - D(rel)) according to Heckel (y) and force presented as pressure (z) were used to plot a graph. A twisted plane was fitted to this three-dimensional plot. This plane was characterized by three parameters d, the slope over time called 'time plasticity', e, the slope over pressure called 'pressure plasticity' and omega, the angle of rotation called 'fast elastic decompression'. These parameters were used to characterize the densification behavior of the well-known materials microcrystalline cellulose, dicalcium phosphate dihydrate, theophylline monohydrate, cellulose acetate and hydroxypropyl methylcellulose at different rho(rel, max). It could be shown that brittle, elastic and plastic compression properties could be very well distinguished and differentiated. Further on, it could be shown whether these properties were due to pressure or time. Thus this model has the prevailing advantage to characterize tableting materials in one step according to time and pressure and it is a useful tool to develop tablet formulations or new excipients.

Topics: Algorithms; Calcium Phosphates; Cellulose; Drug Compounding; Excipients; Hypromellose Derivatives; Methylcellulose; Models, Theoretical; Pressure; Tablets; Theophylline; Time Factors

An injectable composite material based on biphasic calcium phosphate (BCP) and a nonionic cellulose ether has been elaborated for use in percutaneous surgery for spine fusion. This paper reports the characterization results of this material by spectroscopic techniques including X-ray diffraction (XRD), infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) fitted with an energy dispersive X-Ray analysis system and high-resolution transmission electron microscopy (HR-TEM). From FTIR and XPS results, it was observed that the adhesion between the polymer and the ceramic might be insured by oxygen bridging developed through an ionic bonding between calcium ions and (C-O) groups of the polymer. Moreover, XPS showed attraction of Ca2+ ions in the polymer matrix, while the ceramic surface was modified in a HPO4(2-) -rich layer. These results suggest a possible dissolution/precipitation process at the interface ceramic/polymer. HR-TEM observations supported this hypothesis, showing a light contrasted fringe at the surface of the ceramic grains in the composite paste. As well, changes in the XRD spectra could indicate a small decrease in the crystal size of the BCP powder through the contact to polymer solution. In addition, SEM observation showed a decrease of the initial BCP granulometry. Aggregates of 80-200 microm seemed to be mostly dissociated in micrograins. The ceramic grains were coated with and bonded between each other by the polymer matrix, which acted as spacer in between the ceramic grains, creating a macroporous-like material structure.

Topics: Biocompatible Materials; Calcium Phosphates; Ceramics; Chemical Phenomena; Chemistry, Physical; Drug Carriers; Drug Combinations; Electron Probe Microanalysis; Ethers; Hypromellose Derivatives; Injections; Methylcellulose; Microscopy, Electron; Microscopy, Electron, Scanning; Spectroscopy, Fourier Transform Infrared; Sterilization; X-Ray Diffraction

Many different bone substitutes, such as autografts, allografts or synthetic biomaterials have been proposed to restore alveolar bone loss and support efficient placement of dental implants. This experimental study evaluated the osteoconductive properties of an injectable bone substitute (IBS) composed of a polymeric carrier and a calcium phosphate mineral phase, used to fill mandibular and maxillary canine extraction sockets.. The polymer was a cellulose derivative (methyl-hydroxy-propyl-cellulose, MHPC), and the mineral phase consisted of granules of biphasic calcium phosphate (BCP) ceramics 200 to 500 microm in diameter. Mandibular and maxillary premolars extracted from 3 dogs (a total of 60 extraction sites) were immediately treated with the IBS or left unfilled as control sites. Animals were sacrificed 3 months after implantation and all extraction sockets were prepared for histological evaluation.. Qualitative histological studies showed that the IBS was able to support the extensive apposition of well-mineralized newly formed lamellar bone over the entire socket surface and appeared to prevent alveolar ridge bone loss in treated extraction sites. Quantitative evaluation showed that the amount of newly formed bone was significantly higher in mandibular than maxillary extraction sockets for both treated and control sites.. An injectable bone substitute composed of a polymeric carrier and calcium phosphate was effective in enhancing the bone fill of extraction sockets. This approach may prove promising for periodontal lesions. The material expressed osteoconductive capacities, and the biological properties of the mineral phase were conserved.

Topics: Animals; Bone Regeneration; Bone Substitutes; Calcium Phosphates; Ceramics; Dogs; Drug Carriers; Female; Hypromellose Derivatives; Injections; Methylcellulose; Pilot Projects; Statistics, Nonparametric; Tooth Extraction; Tooth Socket

Several sustained-release tablet formulations with acceptable pharmacokinetic properties were found to be unstable because of the effects of lactose. Because the pharmacokinetic properties were acceptable, an attempt was made at developing stable formulations that reproduced the in vitro drug release characteristics of the unstable formulations. Through the use of a statistically designed mixture experiment, alternative formulations were generated and tested for dissolution. The dissolution data collected in the mixture experiment were used to develop a statistical regression model for identifying formulations with dissolution rates equal to those of the unstable formulations. The form of the regression model was based on the Higuchi equation. The data analysis indicated that it is possible to generate dissolution profiles that reproduce those of the original formulations by adjusting the ratios of Methocel K4MCR Premium and Methocel K100MCR Premium and by replacing the detrimental lactose with calcium phosphate dibasic anhydrous.

Topics: Calcium Phosphates; Delayed-Action Preparations; Methylcellulose; Regression Analysis; Solubility; Tablets

The calcium phosphate cement (CPC) used in this study was formed by combining equimolar amounts of tetracalcium phosphate (TTCP) and dicalcium phosphate anhydrous (DCPA). This powder, when mixed with water, sets to a hard cement in about 30 min. However, the water-based CPC paste is not highly cohesive and is vulnerable to washout until hardening occurs. The objectives of this study were to investigate the effects on handling properties, washout resistance, cement hardening behavior, and mechanical properties of adding several gelling agents to CPC paste. Aqueous solutions that contained a mass fraction of 2-4% of hydroxypropyl methylcellulose (HPMC), carboxyl methylcellulose (CMC), chitosan acetate, and chitosan lactate were used as cement liquids. Hardening time was measured by the Gilmore needle test; resistance to washout was evaluated by the disintegration of the cement specimen in water with agitation; and mechanical strength was evaluated by the measurement of diametral tensile strength and compressive strength. Handling properties were greatly improved by the addition of HPMC, CMC, chitosan acetate, and chitosan lactate. Hardening time was retarded by the additions of HPMC and CMC, and mechanical strength was weakened by the addition of either the chitosan lactate or the chitosan acetate.

Topics: Biocompatible Materials; Calcium Phosphates; Carboxymethylcellulose Sodium; Chitin; Chitosan; Dental Cements; Hypromellose Derivatives; Materials Testing; Methylcellulose; X-Ray Diffraction

We report the results obtained by infrared (IR) and X-ray photoelectron spectroscopy (XPS) on the multiphasic composite material formed by the mixture of biphasic calcium phosphate (BCP) and hydroxypropylmethylcellulose (HPMC). This synthetic material, intended for bone substitution, is injectable and allows percutaneous surgery. Core level spectra of carbon, oxygen, calcium, and phosphorus were recorded on separate components before mixing and then compared to those obtained in the final product. Analysis of the spectra shows that formation of calcium carbonate has occurred upon mixing the components in agreement with IR results. An attempt to explain the formation mechanism of the composite is given involving the nature of the constituents on one hand and the possible reactions between the different components on the other.

Topics: Bone Substitutes; Calcium; Calcium Carbonate; Calcium Compounds; Calcium Phosphates; Carbon; Ceramics; Hydrogen-Ion Concentration; Hypromellose Derivatives; Methylcellulose; Oxides; Oxygen; Phosphorus; Polymers; Powders; Spectrophotometry, Infrared