Simon R Bechard

Film coating : effect of titanium dioxide concentration and film thickness on the photostability of nifedipine

Abstract The opacity of film coatings is of particular importance for the stabilization of photosensitive drugs and can be defined by means of a contrast ratio. Films having contrast ratio values of 33% to > 99% were evaluated using a photolabile compound, nifedipine, as a model drug. Titanium dioxide was used as the pigment to impart film opacity and was added at 9.5–29.5% (dry film) levels to HPMC 6 cP films plasticized with PEG 3350 (20%). Films were sprayed onto nifedipine 20 mg tablets at 2–15% weight gains using a Wurster column with a bottom spray configuration. The film thicknesses were evaluated by scanning electron microscopy. The cores and coated tablets were introduced into a light cabinet and exposed to 4.4 klux fluorescent light (Cool White, General Electric) over 21 days. The tablets were sampled at predetermined time points and assayed by HPLC (UV detection at 230 nm) for percent nifedipine remaining. Control samples were also introduced into opened containers and stored in total darkness. The results showed that the film thickness values ranged over 24–145 μm. The films that had contrast ratios values of above 98% imparted good light protection. This was achieved by using a coating that contains 29.5% titanium dioxide with a thickness of 145 μm.

Infrared Imaging of Pharmaceutical Materials Undergoing Compaction

The goal of this study was to use infrared thermography as a new technique to investigate the heat released during compaction and consolidation of pharmaceutical powders and granules. Real-time temperature measurements without physical contact with tablets were provided by a highly sensitive (±0.1°C at 30°C) infrared camera (Agema Infrared Systems, Model 470 with CM-SOFT software). High-resolution images were captured at the takeoff point, i.e., less than 1 sec after compaction, stored on floppy disks, and then analyzed on a regular PC equipped with a VGA color monitor. Thermal surface profiles of tablets were obtained with high geometric and temperature resolution. Reproducibility of the camera readouts was better than 3%. The model granulation used was a direct compression blend of microcrystalline cellulose, spray-dried lactose, and magnesium stearate. This blend was compressed using an instrumented Korsch PH106 rotary press fitted with 1 station of 19.1 × 7.9-mm (0.750 × 0.312-in.) capsule-shaped tools. The effects of compaction force (6–20 kN), rate (130- to 360-msec contact time), and lubricant level (0.5 and 1.0%) on postcompaction temperature rise, caused by heat released during compaction, were investigated. The presence and location of nonhomogeneous heat distribution were assessed as well. Results have shown that the heat released during compaction increases with compaction force. Tablet surface temperatures of 33.8 ± 0.7°C were observed at 20 kN compaction force in contrast to 29.5 ± 0.3°C at 6.7 kN. The compression rate, as determined by the upper punch contact time did not have any significant effect on the heat released during compaction at 15-kN force. However, magnesium stearate level had a significant effect on the heat released during a compaction run. Tablets lubricated with 1.0% magnesium stearate had surface temperatures of 39–40°C after a 20-min run time, as opposed to 50–51°C for tablets lubricated with 0.5% magnesium stearate. Hot spots were seen at tablet edges where the die-wall friction occurs. Tablet cross-sectional thermal profiles revealed a 3–4°C temperature gradient across the tablet. These experiments show that infrared imaging is a unique tool for semiquantitative evaluation of heat released during compaction because it provides direct visualization with good temperature resolution of the heat evolved during the process.

Thermal, mechanical and functional properties of cellulose acetate phthalate (CAP) coatings obtained from neutralized aqueous solutions

Abstract This study investigated the thermal, mechanical and functional properties of cellulose acetate phthalate (CAP) film coatings obtained from neutralized aqueous solutions. A novel salt forming agent, 2-amino-2-methyl-l-propanol (MAP), was used for the neutralization and dissolution of CAP in water. Triethylcitrate (TEC) was used as the plasticizer at 10–35% levels. Thermal and mechanical properties of free films plasticized with 10–35% TEC were evaluated by thermogravimetric analysis (TGA), thermal mechanical analysis (TMA) and dynamic mechanical spectroscopy (DMS). The physical stability of CAP/MAP films stored at 40 and 50°C was compared to ammoniated CAP films with respect to dissolution times in pH 6.8 buffer. Plasticized CAP/MAP films were also sprayed at three weight gains (6, 8 and 10%) onto acetylsalicylic acid (ASA) tablets (650 mg) using pan coating technology. The functional properties of the films were assessed for enteric integrity in 0.1 N HCI, drug release in pH 6.8 phosphate buffer and water permeability. Results have shown that CAP/MAP films plasticized with 25–35% TEC released ≤1% ASA after 2 h in 0.1 N HCl and > 95% after 1 h in buffer, thereby demonstrating their excellent functional properties. These films had high permeability to water/acid which makes them unsuitable for acid-labile drugs, since water/HCl would penetrate rapidly into the tablet core and degrade the drug. Neither the T g nor E ′ values differed significantly for films that showed satisfactory functional properties. Films were stiff and brittle with E ′ values in the range of 2–3 × 10 9 Pa and T g values of 108–112°C. TEC appeared to have limited solubility in the CAP/MAP polymer with reduced plasticization effects at concentrations higher than 20–25%. CAP/MAP free films were found to be superior to ammoniated CAP films with respect to extent of aging when stored at 40°C. The results clearly showed the potential use of plasticized CAP/MAP films as an enteric film former for pharmaceutical products.