Conceptualisation, Development, Fabrication and In Vivo Validation of a Novel Disintegration Tester for Orally Disintegrating Tablets

Disintegration time is the key critical quality attribute for a tablet classed as an Orally Disintegrating Tablet (ODT). The currently accepted in vitro testing regimen for ODTs is the standard United States Pharmacopeia (USP) test for disintegration of immediate release tablets, which requires a large volume along with repeated submergence of the dosage form within the disintegration medium. The aim of this study was to develop an in vivo relevant ODT disintegration test that mimicked the environment of the oral cavity, including lower volume of disintegration medium, with relevant temperature and humidity that represent the conditions of the mouth. The results showed that the newly developed Aston test was able to differentiate between different ODTs with small disintegration time windows, as well as between immediate release tablets and ODTs. The Aston test provided higher correlations between ODT properties and disintegration time compared to the USP test method and most significantly, resulted in a linear in vitro/in vivo correlation (IVIVC) (R 2 value of 0.98) compared with a "hockey stick" profile of the USP test. This study therefore concluded that the newly developed Aston test is an accurate, repeatable, relevant and robust test method for assessing ODT disintegration time which will provide the pharmaceutical industry and regulatory authorities across the world with a pragmatic ODT testing regime

Comparative analysis of co-processed starches prepared by three different methods

Co-processing is currently of interest in the generation of high-functionality excipients for tablet formulation. In the present study, comparative analysis of the powder and tableting properties of three co-processed starches prepared by three different methods was carried out. The co-processed excipients consisting of maize starch (90%), acacia gum (7.5%) and colloidal silicon dioxide (2.5%) were prepared by co-dispersion (SAS-CD), co-fusion (SAS-CF) and co-granulation (SAS-CG). Powder properties of each co-processed excipient were characterized by measuring particle size, flow indices, particle density, dilution potential and lubricant sensitivity ratio. Heckel and Walker models were used to evaluate the compaction behaviour of the three co-processed starches. Tablets were produced with paracetamol as the model drug by direct compression on an eccentric Tablet Press fitted with 12 mm flat-faced punches and compressed at 216 MPa. The tablets were stored at room temperature for 24 h prior to evaluation. The results revealed that co-granulated co-processed excipient (SAS-CG) gave relatively better properties in terms of flow, compressibility, dilution potential, deformation, disintegration, crushing strength and friability. This study has shown that the method of co-processing influences the powder and tableting properties of the co-processed excipient

Comparative analysis of co-processed starches prepared by three different methods

Co-processing is currently of interest in the generation of high-functionality excipients for tablet formulation. In the present study, comparative analysis of the powder and tableting properties of three co-processed starches prepared by three different methods was carried out. The co-processed excipients consisting of maize starch (90%), acacia gum (7.5%) and colloidal silicon dioxide (2.5%) were prepared by co-dispersion (SAS-CD), co-fusion (SAS-CF) and co-granulation (SAS-CG). Powder properties of each co-processed excipient were characterized by measuring particle size, flow indices, particle density, dilution potential and lubricant sensitivity ratio. Heckel and Walker models were used to evaluate the compaction behaviour of the three co-processed starches. Tablets were produced with paracetamol as the model drug by direct compression on an eccentric Tablet Press fitted with 12 mm flat-faced punches and compressed at 216 MPa. The tablets were stored at room temperature for 24 h prior to evaluation. The results revealed that co-granulated co-processed excipient (SAS-CG) gave relatively better properties in terms of flow, compressibility, dilution potential, deformation, disintegration, crushing strength and friability. This study has shown that the method of co-processing influences the powder and tableting properties of the co-processed excipient

Co-Processed Excipients for Dispersible Tablets–Part 1: Manufacturability

Co-processed excipients may enhance functionality and reduce drawbacks of traditional excipients for the manufacture of tablets on a commercial scale. The following study aimed to characterise a range of co-processed excipients that may prove suitable for dispersible tablet formulations prepared by direct compression. Co-processed excipients were lubricated and compressed into 10.5-mm convex tablets using a Phoenix compaction simulator. Compression profiles were generated by varying the compression force applied to the formulation and the prepared tablets were characterised for hardness, friability, disintegration and fineness of dispersion. Our data indicates that CombiLac, F-Melt type C and SmartEx QD100 were the top 3 most suitable out of 16 co-processed excipients under the conditions evaluated. They exhibited good flow properties (Carr’s index ˂ 20), excellent tabletability (tensile strength > 3.0 MPa at 0.85 solid fraction), very low friability (< 1% after 15 min), rapid disintegration times (27–49 s) and produced dispersions of ideal fineness (< 250 μm). Other co-processed excipients (including F-Melt type M, Ludiflash, MicroceLac, Pharmaburst 500 and Avicel HFE-102) may be appropriate for dispersible tablets produced by direct compression providing the identified disintegration and dispersion risks were mitigated prior to commercialisation. This indicates that robust dispersible tablets which disintegrate rapidly could be manufactured from a range of co-processed excipients