Evaluation of two novel co-processed excipients for direct compression of orodispersible tablets and mini-tablets.

Pediatric, geriatric, and other patients who suffer from swallowing difficulties represent a special patient group, where an increased need in appropriate formulation development is required. To overcome these mostly swallowability linked issues, orodispersible tablets (ODTs) and orodispersible mini-tablets (ODMTs) can be seen as a suitable alternative to improve compliance. Orodispersible tablets are oral solid dosage forms which rapidly disintegrate after contact with saliva, leaving a liquid dispersion, which can be easily swallowed. To fulfil the required quality criteria and optimize the formulations regarding tensile strength and disintegration time, co-processed excipients (CPE) based on mannitol are frequently used in the manufacturing of orodispersible tablets. This study aimed to systematically compare two new CPEs, namely Granfiller-D® and Hisorad® and evaluate their potential in future OD(M)T formulations with already marketed products. The performance of the CPEs was examined in combination with three different APIs. Disintegration time, sufficient mechanical strength and content uniformity for low dosed formulation were chosen as main quality aspects. Conventionally sized tablets (9 mm) with 50% drug load of ibuprofen and paracetamol were produced with each CPE. Low dosed OD(M)Ts with a drug load of 4% enalapril maleate were manufactured to study content uniformity. Large differences were visible in the formulations containing ibuprofen and only Hisorad® allowed to compress ODT fulfilling the specifications of Ph.Eur. and FDA regarding disintegration times (180 s and 30 s, respectively). For the poorly binding model drug paracetamol, none of the studied excipients showed a satisfactory performance, with maximum tensile strengths < 1 MPa. To reach content uniformity in low dosed ODMTs, Ludiflash® seems to be the most preferable alternative, as the formulation showed the lowest acceptance values (AV) according to Ph.Eur. (<4) as well as the smallest coefficient of variation (CV) in API content (CV < 2%). In conclusion, the study revealed that none CPE is the ideal choice for all approaches, but different CPEs should be selected dependent on different challenges during formulation development of OD(M)Ts.