PHARMACOTECHNICAL DEVELOPMENT AND OPTIMIZATION OF MULTILAYERED TABLETS: AN UPDATED INDUSTRIAL REVIEW WITH EMPHASIS ON BILAYER TABLETS

Fixed-dose combination formulations are multilayered platforms designed for solving complex medication regimens and overcoming polypharmacy problems especially in chronic diseases with geriatric patients. Multilayered tablets are considered promising avenues to combine different active pharmaceutical ingredients (APIs) for a synergic therapeutic effect, or different formulations of the same API in order to achieve a specific drug release profile. Besides, multilayered tablets can extensively help in avoiding possible interactions between different drugs, as well as optimizing each formulation individually in terms of pharmacokinetics and manufacturability. This review article discusses the most suitable materials used in the manufacturing of multilayered tablets, describes novel approaches to manufacturing improvement and process parameters, the influence of process parameters on layer adhesion, and the characterization tests of multilayered tablets

FORMULATION AND CHARACTERIZATION OF ODT USING DIFFERENT CO-PROCESS CONTAINNG DACLATSVIR: IN VITRO AND IN VIVO PHARMACOKINETICS STUDY ON HEALTHY VOLUNTEERS FOR HEPATITIS C TREATMENT

Objective: This study aimed to prepare and evaluate oral disintegrating tablets (ODTs) of Daclatasvir dihydrochloride (DCV) using different co-processed excipients to enhance drug dissolution and improve oral bioavailability for treatment of hepatitis C infection. Methods: Ten Daclatasvir-ODTs formulae were prepared using co-processed excipients via direct compression. The prepared formulae were evaluated according to taste masking, weight variation, thickness, friability, hardness, drug content, and wetting time. In-vitro disintegration time, in-vivo disintegration time, and in-vitro dissolution tests were also evaluated and taken as parameters for the selection of the best formula. The selected best formula was subjected to an in-vivo study on volunteers and compared to a marketed product. Results: All DCV-ODTs had acceptable physical properties in accordance with pharmacopeial standards. DCV-ODTs prepared with Pharmaburst® (F10) recorded the shortest wetting time (14±0.08s), fastest invitro disintegration time (46±0.16s), shortest in-vivo disintegration time (27±0.16s), and attained the fastest onset of dissolution (94.3±0.03 %) at 5 min to all other excipients and has been identified as the best formula. The in-vivo pharmacokinetic study showed that Pharmaburst-based formula has a significant Cmax increase of (2.17 ± 0.28 μg/ml) compared to (1.42±0.59) for the marketed product and a significant decrease of Tmax to 60 min instead of 110 min for the marketed product. Conclusion: The in-vivo pharmacokinetic study in humans showed that the ODTs was found to be appropriate for delivery of Daclatasvir with a faster drug absorption rate when compared to the marketed products with applicable taste related to the nature of dosage form