Doctor Dissertation Of Ha Nguyen Thi Hong

Dissertation: “A fast release paracetamol tablet: Formulation, pharmaceutical process and bioavailability”.

Dissertation: “A fast release paracetamol tablet: Formulation, pharmaceutical process and bioavailability”

Specialized in: Pharmaceutics

Name of candidate: Nguyen Thi Hong Ha

Under the scientific supervision of:

1. Ass. Prof, Dr: Nguyen Dang Hoa

2. Ass. Prof, Dr: Nguyen Van Long

Institution: Ha Noi University of Pharmacy

Summary of new aspects of the thesis:

- This research have designed formulation and pharmaceutical process for fast release tablets of paracetamol on 30000 tablet-scale manufacture. The designed formulation and pharmaceutical process are simple and effective with the wet granulating method for paracetamol and sodium bicarbonate individually was advantage on fast release paracetamol from tablet and on stability of paracetamol. The designed formulation and pharmaceutical process for fast release tablet of paracetamol were simply and easy to develop to other drugs those efficacy depend on the rate of drug release from tablets.

- The pharmaceutical process of studied fast release tablets named Paracetamol FR was validated by operating three continuous batches to ensure and provide documentary evidence that were capable of consistently producing of finished product of the required quality.

- The quality control of new fast release paracetamol tablet formulations has been standardized and documented. All measures taken, including the setting of specifications, sampling, testing and analysis have been verified by National Institute of Drug Quality Control.

- Aluminium foil packaged fast release paracetamol tablets were stable for 6 months stored at accelerated condition and 24 months at lab condition. According to FDA method, the self-life of study product has been estimated 32 months.

- The bioavailability of paracetamol from studied fast release tablets named Paracetamol FR compared to marketed products as references after single oral dose (500 mg) administration was determined in 18 fasted healthy volunteers using a randomized crossover design. In this study, Paracetamol FR has following pharmacokinetic properties: C_max=32,7±12,1(µg/ml), AUC_0-600=3767±1391 (µg/ml*min.), AUC_0-∞=4110±1731(µg./ml*min.), T_max=19±13 (min.). It was stated thatParacetamol FR was bioequivalent to rapidly absorbed reference as Panadol actifast that manufactured by GlaxoSmithKline, with respect to area under the curve (AUC), maximum concentration (C_max) and time to maximum concentration (T_max). As well as the results demonstrated that paracetamol was absorbed more rapidly from Paracetamol FR compared to Panadol 500 mg, as indicated by a shorter T_max(p = 0,002) and higher C_max(p = 0,057 ; CI = 103,1 ; 133,1%). The in vivo bioavailability data showed that Paracetamol FR was fast released and rapidly absorbed tablet.

The scientific advisors

Ass. Pro. Dr. Nguyen Dang Hoa Ass. Pro. Dr. Nguyen Van Long

Doctorate candidate

MSc. Nguyen Thi Hong Ha

Dissertation Abstract_ Ha Nguyen Thi Hong.doc