Characterisation and evaluation of pregelatinised sago starch as direct compression materials / Riyanto Teguh Widodo

• 主要作者: Widodo, Riyanto Teguh
• 格式: Thesis
• 出版: 2014
• 主題: R Medicine (General)

This study aimed to produce new directly compressible materials from a local sago starch. The sago starch was pregelatinised at 65°C with four different heating times followed by oven drying. The pregelatinised sago starches (PS) were evaluated as directly compressible materials including their properties at molecular, particle and powder level in addition to their functional properties in directly compressible Paracetamol tablet formulations. Analysis of FT-IR and 13CNMR spectra revealed that pregelatinisation did not alter the chemical structure of sago starch. XR-D patterns of sago starch showed characteristics of C-type while PS exhibited A-type, as the degree of crystallinity decreased with increasing heating time. DSC curves showed pregelatinisation increased gelatinisation temperature (To), peak temperature (Tp), and degree of gelatinisation (DG), narrowed gelatinisation temperature range (Tc – To) and decreased the melting enthalpy (ΔH) of sago starch, becoming more pronounced with increased heating time. SEM observations showed more sago starch granules lost their surface smoothness and more irregular shapes appeared as the heating time increased. PS showed higher swelling power (SP) at ≤ 55˚C and water solubility index (WSI) at ≤ 65˚C than sago starch. Longer heating time produced PS with lower amylosa content, higher viscosity, SP and WSI. Powder flow evaluations and powder compacts analysis by Heckel and Kawakita equations, mechanical properties and lubricant sensitivity revealed pregelatinisation improved flowability, compressibility, compactibility and lubricant sensitivity of sago starch, with the order PS4>PS3>PS2>PS1>sago starch. PS4 flowability, compressibility and compactibility was comparable to Spress® B820 but showed lower lubricant sensitivity. Compared to Avicel PH 101, PS4 flowability was superior but its compressibility, compactibility and lubricant sensitivity were inferior. Based on the findings, PS4 was the best candidate for directly compressible excipient iv among PS. Evaluation on the loading capacities for Avicel PH 101, PS4 and Spress® B820 relative to poorly compressible Paracetamol reached up to 70.16%, 60.97% and 59.16% W/W respectively. Paracetamol tablets formulated with Avicel PH 101 (Formulation 1) showed the fastest disintegration times, followed by those formulated with PS4 (Formulation 3) and Spress® B820 (Formulation 2) with disintegration times less than 2 minutes, indicating good disintegration properties. However, Formulation 1 did not release 80% of Paracetamol within 30 minutes as required by the USP 27. Dissolution profiles of Formulation 2 and Formulation 3 were similar, releasing > 80% of Paracetamol within 20 minutes and completely releasing of Paracetamol within 25 minutes. Introducing Avicel PH 101 and Sodium starch glycolate in Formulation 2 and Formulation 3, hence identified as Formulation 4 and 5 respectively, showed significantly shortened disintegration times and released > 80% of Paracetamol within 5 minutes. Formulation 4 and Formulation 5 released 100% and 99.95% of Paracetamol respectively within 15 minutes. Their dissolution efficiencies differ by 0.19%, indicating similar dissolution profiles and bio-equivalency. Results of accelerated stability study at conditions of 40C ± 2C / 75% RH ± 5% RH for 3 months and 6 months storage showed Formulations 4 and 5 were stable. As a conclusion, this study found that PS4 has the potential as a directly compressible excipient and its characteristics and performances were comparable to Spress® B820.