Flösser A, Kolter K, Reich H B, Schepky G
Fachhochschule, Pharmatechnik Department, Sigmaringen, Germany.
Drug Dev Ind Pharm. 2000 Feb;26(2):177-87. doi: 10.1081/ddc-100100342.
Using a formulation described previously with Kollicoat MAE 30 D as the film-forming agent, the effect of variations in plasticizer type and quantity and talc concentration on the preparation and processing of spray-coating suspensions and the properties of isolated films and film-coated caffeine tablets prepared using them was investigated. In the preparation and processing of spray-coating suspensions, the plasticizers polyethylene glycol (PEG) 400, PEG1500, and TEC (triethyl citrate) tended to coagulate at all concentrations investigated, while Cremophor RH 40 coagulated above 10% (expressed as a percentage of the mass of the film-forming agent used). Analogous preparations using propylene glycol (PG), PEG6000, and Lutrol F 68, on the other hand, were found to be stable at all concentrations. The instability was not caused by the Kollicoat MAE 30 D polymer dispersion as such, but by interactions between the finely dispersed pigments and other formulation ingredients. Equivalent nonpigmented preparations are stable and do not coagulate. With all the plasticizers investigated, the minimum film-forming temperature (MFT) fell, albeit to differing degrees, as the amount of plasticizer increased. Similarly, the tensile strength of isolated films declined as plasticizer concentration increased, while the reverse was true as regards their elongation at break. Whereas neither the subsequent disintegration time nor the rate of release of active ingredient at pH 6.8 was significantly affected by the various plasticizer additives, the different film-coated tablet formulations with a core containing a powerful disintegrant exhibited varying degrees of permeability to simulated gastric fluid. With PEG6000, permeability increased as the plasticizer concentration increased, while Lutrol F 68 provided an optimum barrier at 20%, and PG provided a good barrier between 10% and 30%. No gastroresistance was obtained with TEC at 10%. Only the best plasticizer formulations were used in the trials with different talc concentrations, namely, those formulations with 20% PEG6000, 20% Lutrol F 68, 20% PG, and 10% PG. When talc was added, the MFT rose, reaching its maximum at 13% talc (as a proportion of the film-forming agent). In the test for gastroresistance, film-coated caffeine tablets without talc absorbed distinctly more acid than those containing talc. Above 27% talc, the acid resistance improved only insignificantly. On the other hand, during this test, only a maximum of 3% of the active ingredient was released into the gastric juice. Of the variants investigated, the formulation with 20% PG and 27% talc performed best.
使用先前描述的以Kollicoat MAE 30 D为成膜剂的配方，研究了增塑剂类型和用量以及滑石粉浓度的变化对喷雾包衣悬浮液的制备和加工以及使用它们制备的分离膜和薄膜包衣咖啡因片剂性能的影响。在喷雾包衣悬浮液的制备和加工过程中，增塑剂聚乙二醇（PEG）400、PEG1500和柠檬酸三乙酯（TEC）在所有研究浓度下都趋于凝结，而聚氧乙烯蓖麻油RH 40在高于10%（以所用成膜剂质量的百分比表示）时会凝结。另一方面，使用丙二醇（PG）、PEG6000和聚山梨酯F 68的类似制剂在所有浓度下均稳定。这种不稳定性不是由Kollicoat MAE 30 D聚合物分散体本身引起的，而是由细分散的颜料与其他配方成分之间的相互作用引起的。等效的无色素制剂是稳定的，不会凝结。对于所有研究的增塑剂，随着增塑剂用量的增加，最低成膜温度（MFT）均下降，尽管下降程度不同。同样，分离膜的拉伸强度随着增塑剂浓度的增加而下降，而其断裂伸长率则相反。虽然各种增塑剂添加剂对随后的崩解时间和在pH 6.8下活性成分的释放速率均无显著影响，但含有强力崩解剂的不同薄膜包衣片剂配方对模拟胃液的渗透性各不相同。对于PEG6000，渗透性随着增塑剂浓度的增加而增加，而聚山梨酯F 68在20%时提供了最佳屏障，PG在10%至30%之间提供了良好的屏障。10%的TEC未获得抗胃酸能力。在不同滑石粉浓度的试验中，仅使用了最佳的增塑剂配方，即含有20% PEG6000、20%聚山梨酯F 68、20% PG和10% PG的配方。添加滑石粉后，MFT升高，在滑石粉含量为13%（占成膜剂的比例）时达到最大值。在抗胃酸试验中，不含滑石粉的薄膜包衣咖啡因片剂比含滑石粉的片剂吸收的酸明显更多。滑石粉含量高于27%时，耐酸性仅略有改善。另一方面，在该试验中，活性成分释放到胃液中的量最多仅为3%。在所研究的变体中，含有20% PG和27%滑石粉的配方表现最佳。
