Category: Formulation and Quality
Purpose: An effective drug treatment for peptic ulcer and reflux esophagitis is the proton pump inhibitor (PPI). Lansoprazole is a PPI-based drug and its therapeutic effect is excellent. Despite the excellent therapeutic effect, however, the lansoprazole is very sensitive to acidic decomposition and has a difficulty in commercializing due to the problem of re-precipitation. Therefore an enteric solute capsule was prepared using sodium alginate and wet granulation process. This formulation aimed to inhibit release in acidic conditions of stomach fluid and to cause rapid drug release under conditions of intense, neutral or weakly alkaline conditions.
Methods: Lansoprazole and sodium alginate for drug inclusion were added in the same ratio, and MCC, SSG and L-HPC were added by disintegration, PVP K30 was added as a binder and mixed uniformly. The mixed mixture was wet granulated by adding 50μl of 10% aquaous ethanol solution 10 times. The granules were then filtered using a 600μm mesh and dried in an oven. The hard capsules were filled with the granules according to the total amount of each batch and used for the dissolution test. DSC analysis was conducted to determine the thermal transfer of lansoprazole and sodium alginate used in the inclusion and to confirm that the granules were normally. Crystallinity was analyzed by XRD in order to confirm whether the granules were folded normally. Lansoprazole, sodium alginate and the molecular structure of each prepared granulate was analyzed and analyzed using FT-IR to confirm that a new chemical bond was generated. The particle status and surface of the raw drug, sodium alginate and granules were analyzed using scanning electron microscope. The dissolution test was conducted to evaluate the dissolution rate and analyzed by HPLC.
Results: As a result of the structural analysis of the granules using FT-IR, we investigated what kind of chemical bonds they encapsulate in the process of embedding sodium. In all samples, the intensity of the peak of 3000 ~ 3600 cm-1 was decreased, and it was found that the hydrogen bonding behaved by moving to the lower wave number. In DSC, all batches does not show peak of lansoprazole, due to encapsulate of sodium alginate. Therefore, it can be confirmed that the collapse of the lidocaine is due to the hydrogen bonding of lansoprazole and sodium alginate. As the ratio of sodium alginate is increased, the intrinsic peak of sodium alginate is clearly observed. This confirms that lansoprazole is normally contained in the sodium alginate by the wet granulation process. In the case of XRD analysis, the amount of sodium alginate gradually increased from batch 1 to batch 5, so that the peak of the drug also decreased slightly. Therefore, it can be seen that when the amount of sodium alginate is increased, the incorporation rate of the drug is slightly increased. All samples were observed through SEM observation. In batch 1, the ratio of sodium alginate to lansoprazole was small and the number of normal granules was small. As the ratio increased to batch 5, the particle size of the granules was large and the crystals of unincorporated lansoprazole were few. As the ratio of alginate increased, granule formation occurred well and granule particles of uniform size were observed. In case of hard capsules filled with lansoprazole alone, the dissolution test was up to 26% in gastric conditions. In serous conditions, the higher the ratio of sodium alginate in the granules, the slower the release of the drug and the higher the final dissolution rate.
Conclusion: The wet granules can form granules due to the hydrogel bonding of lansoprazole and sodium alginate, and it is possible to see whether the granules are formed normally through DSC and XRD. The crystals of lansoprazole remained in the granules could be observed by the SEM photograph as the sodium alginate increased. In addition, the dissolution rate was more than 10% due to the addition of sodium alginate, and the release of the drug was inhibited under acidic conditions.
Min Rim– Jeonju-si, Cholla-bukto, Republic of Korea
Won Kyung Kim– Jeon Ju, Cholla-bukto, Republic of Korea
Jeong Eun Song– Jeon Ju, Cholla-bukto, Republic of Korea
Gilson Khang– Jeon Ju, Cholla-bukto, Republic of Korea
Min A Rim– Student, Jeon Buk National Univ., Jeon Ju, jeon ju, Korea, Republic Of