Garnet E. Peck

Physical properties and molecular behavior of chitosan films.

Chitosan films, varying in molecular weight and degree of deacetylation, were prepared by a casting technique using acetic acid as a dissolving vehicle. The physicochemical properties of the films were characterized. Both molecular weight and degree of deacetylation affected the film properties. Powder X-ray diffraction patterns and differential scanning calorimetry thermograms of all chitosan films indicated their amorphous state to partially crystalline state with thermal degradation temperature lower than 280–300°C. The increase in molecular weight of chitosan would increase the tensile strength and elongation as well as moisture absorption of the films, whereas the increase in degree of deacetylation of chitosan would either increase or decrease the tensile strength of the films depending on its molecular weight. Moreover, the higher the degree of deacetylation of chitosan the more brittle and the less moisture absorption the films became. All chitosan films were soluble in HCl–KCl buffer (pH 1.2), normal saline, and distilled water. They swelled in phosphate buffer (pH 7.4), and cross-linking between chitosan and phosphate anions might occur. Finally, transmission infrared and 13C-NMR spectra supported that chitosan films prepared by using acetic acid as a dissolving were chitosonium acetate films.

Drug physical state and drug–polymer interaction on drug release from chitosan matrix films

Four different grades of chitosan varying in molecular weight and degree of deacetylation were used to prepare chitosan films. Salicylic acid and theophylline were incorporated into cast chitosan films as model acidic and basic drugs, respectively. Crystalline characteristics, thermal behavior, drug-polymer interaction and drug release behaviors of the films were studied. The results of Fourier transform infrared and solid-state 13C NMR spectroscopy demonstrated the drug-polymer interaction between salicylic acid and chitosan, resulting in salicylate formation, whereas no drug-polymer interaction was observed in theophylline-loaded chitosan films. Most chitosan films loaded with either salicylic acid or theophylline exhibited a fast release pattern, whereas the high viscosity chitosan films incorporated with salicylic acid showed sustained release patterns in distilled water. The sustained release action of salicylic acid from the high viscosity chitosan films was due to the drug-polymer interaction. The mechanism of release was Fickian diffusion control with subsequent zero order release. It was suggested that the swelling property, dissolution characteristics of the polymer films, pK(a) of drugs and especially drug-polymer interaction were important factors governing drug release patterns from chitosan films.

Quantitative analysis of film coating in a pan coater based on in-line sensor measurements.

A method was developed that enables in-line analysis of film coating thickness on tablets during a pan coating operation. Real-time measurements were made using a diffusereflectance near-infrared (NIR) probe positioned inside the pan during the coating operation. Real-time spectra of replicate batches were used for modeling film growth. Univariate analysis provided a simple method for in-line monitoring of the coating process using NIR data. An empirical geometric 2-vector volumetric growth model was developed, which accounts for differential growth on the face and band regions of biconvex tablets. The thickness of the film coat was determined by monitoring the decrease of absorption bands characteristic of a component of the tablet core and monitoring the increase of bands characteristic of a component in the coating material. There was good correlation between values estimated from the NIR data and the measured tablet volumetric growth. In-line measurements allow the coating process to be stopped when a predetermined tablet coating thickness is achieved.

Solid-state nuclear magnetic resonance (NMR) spectra of pharmaceutical dosage forms

Solid-state 13C NMR spectra of tablets or capsules of prednisolone, enalapril maleate, lovastatin, simvastatin, ibuprofen, flurbiprofen, mefenamic acid, indomethacin, diflunisal, sulindac, and piroxicam were obtained in the CP/MAS mode at 50 MHz. These studies show that (1) solid-state NMR spectroscopy can detect the active ingredients in low-dose tablets and capsules; (2) the use of interrupted decoupling often results in suppression of resonances due to excipients, thereby allowing better detection of resonances from the drug; and (3) the technique permits discrimination between two prednisolone polymorphs present in tablets obtained from various manufacturers even though the tablets contain only approximately 5% (w/w) of the drug.

Advances in pharmaceutical materials and processing

Abstract Advances in pharmaceutical materials and processing require new generations of pharmaceutical technologies, which in turn require an improved understanding of each step in the unit processes of dosage form development. The unit processes range from raw material qualification to final product release using process monitoring of critical steps. The authors illustrate some recent research trends in understanding and improving pharmaceutical materials and processing through the use of experience obtained within several research programs at Purdue University (West Lafayette, IN, USA).

Modeling and Monitoring of Polymorphic Transformations During the Drying Phase of Wet Granulation

AbstractPurpose. The purpose of this work was to monitor polymorphic transformations of glycine during the drying phase of a wet granulation and model the polymorphic conversions using a time-based reconciliation model. Methods. Near-infrared spectroscopy (NIR) was used for quantitation of polymorphs, and X-ray powder diffraction (XRPD) was used for qualitative analysis of polymorphs. Results. The data show that the faster the granulation was dried, the more kinetic trapping of the metastable α-glycine polymorph, as predicted by reconciliation of the time scales of both the drying rate and the rate of the solution-mediated conversion. Conclusions. By knowing basic properties of the drug substance (solubility of the polymorphic forms and the rate of the solution-mediated conversion), processing conditions, such as the drying rate, can be adjusted to anticipate and prevent potential polymorphic transformations.

Effects of changes in roller compactor parameters on granulations produced by compaction

AbstractA Chilsonator (Model L-83, The Fitzpatrick Company, Elmhurst, IL) was studied to gain a better understanding of how compactor parameters influence product characteristics. The materials chosen for this study were Avicel PH 101, hydrous lactose and an acetaminophen blend. The blend consisted of 20% Avicel PH 101, 20% hydrous lactose and 60% acetaminophen crystals. The compactor parameters studied were the roll speed, horizontal feed speed and vertical feed speed. Various combinations of high, medium and low levels of these compactor parameters were tested. The system was modeled using a quadratic regression model. Changes in particle size distribution and recompressibility of the roller compacted granulations were used to monitor the effects of the changes in compactor parameter levels. The models differed for each of the materials evaluated. The response surface plots produced using the models helped in predicting the compactor parameter levels which would produce granulations with the necessary p...

Accelerated fluid bed drying using NIR monitoring and phenomenological modeling

A “fast-drying” method to accelerate the fluid bed drying process is presented. It relies on concepts of heat and mass transfer with real-time near-infrared (NIR) monitoring of moisture. Triplicate trials show that fast drying can reduce granulation drying time by half over single-temperature cycles. The product is equivalent in every way tested to material made using a conventional cycle even though the inlet temperature throughout the constant-rate stage was higher than the melting point of the compound. Tablets made from the fast-dried granulation exhibit equivalent physical characteristics to tablets made from granulations dried at a single, lower temperature.

The Effect of the Variability in the Physical and Chemical Properties of Magnesium Stearate on the Properties of Compressed Tablets

AbstractA series of magnesium stearate samples, supplied by foreign and domestic manufacturers, were characterized by their physical and chemical properties. The results Indicated that the samples differed significantly with respect to chemical purity, particle size and surface area. The properties of magnesium stearate lots, manufactured by the same company, were very similar. Whatever variation that was seen was principally due to different suppliers.Microcrystall1ne cellulose tablet formulations were prepared and evaluated using samples of magnesium stearate obtained from 16 sources. Differences 1n tablet quality were observed 1n regard to bulk volume of the blends, tablet tensile strength, and tablet friability. The data revealed that the smaller particle sized magnesium stearate samples (2.4–7.0 μm), with a large surface area (10.6–14.8 m2/g), had the most detrimental effects on the physical properties of mlcrocrystalHne cellulose tablets. Regression analysis and modeling was used to define quantltat...

Quantitative determination of polymorphic composition in intact compacts by parallel-beam X-ray powder diffractometry

This paper details the development of a method using parallel-beam X-ray powder diffractometry as a novel means of determining polymorphic composition in intact compacts. Two polymorphic systems, chlorpropamide and glycine, were selected. The polymorphic components were weighed, mixed, and compressed using a Carver press with 3/8-in. concave tooling. The compacts were then analyzed using parallel-beam X-ray powder diffractometry in transmission geometry. The data were processed using the profile-fitting module in the Shimadzu XRD-6000 software V 4.1 (for NT 4.0/98). The integrated intensity ratio of a selected peak for each crystal form was used for quantitation of each polymorph. Excellent linear correlation was observed for both polymorphic systems. The convex shape of the compact surface had no effect on the XRD patterns. Since parallel-beam X-ray diffractometry is not sensitive to the shape of the sample surface, it provides a simple method for quantifying polymorphs in intact compacts. Further work to extend this to formulated tablets is ongoing. The relatively larger variation in one of the peaks in the chlorpropamide study was found to be consistent with the computational analysis of the slip behavior of the stable polymorph. This method provides the first reported non-invasive X-ray diffraction pattern quantitation of crystal forms in intact compacts.