PMID- 35631478
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 1999-4923 (Print)
IS  - 1999-4923 (Electronic)
IS  - 1999-4923 (Linking)
VI  - 14
IP  - 5
DP  - 2022 Apr 19
TI  - Development of Extended-Release Mini-Tablets Containing Metoprolol Supported by 
      Design of Experiments and Physiologically Based Biopharmaceutics Modeling.
LID - 10.3390/pharmaceutics14050892 [doi]
LID - 892
AB  - The development of extended-release dosage forms with adequate drug release is a 
      challenge for pharmaceutical companies, mainly when the drug presents high 
      solubility, as in Biopharmaceutics Classification System (BCS) class I. This 
      study aimed to develop extended-release mini-tablets containing metoprolol 
      succinate (MS), while integrating design of experiments (DOE) and physiologically 
      based biopharmaceutics modeling (PBBM), to predict its absorption and to run 
      virtual bioequivalence (VBE) studies in both fasted and fed states. Core 
      mini-tablet formulations (F1, F2, and F3) were prepared by direct compression and 
      coated using nine coating formulations planned using DOE, while varying the 
      percentages of the controlled-release and the pore-forming polymers. The coated 
      mini-tablets were submitted to a dissolution test; additional formulations were 
      prepared that were optimized by simulating the dissolution profiles, and the best 
      one was submitted to VBE studies using GastroPlus((R)) software. An optimized 
      formulation (FO) containing a mixture of immediate and extended-release 
      mini-tablets showed to be bioequivalent to the reference drug product containing 
      MS when running VBE studies in both fasted and fed states. The integration of DOE 
      and PBBM showed to be an interesting approach in the development of 
      extended-release mini-tablet formulation containing MS, and can be used to 
      rationalize the development of dosage forms.
FAU - Issa, Michele Georges
AU  - Issa MG
AUID- ORCID: 0000-0002-6099-3687
AD  - Department of Pharmacy, Faculty of Pharmaceutical Sciences, Universidade de Sao 
      Paulo-USP, Av. Prof. Lineu Prestes 580, Sao Paulo 05508-080, SP, Brazil.
FAU - de Souza, Natalia Vieira
AU  - de Souza NV
AD  - Department of Pharmacy, Faculty of Pharmaceutical Sciences, Universidade de Sao 
      Paulo-USP, Av. Prof. Lineu Prestes 580, Sao Paulo 05508-080, SP, Brazil.
FAU - Jou, Bruna Wenyi Chuang
AU  - Jou BWC
AD  - Department of Pharmacy, Faculty of Pharmaceutical Sciences, Universidade de Sao 
      Paulo-USP, Av. Prof. Lineu Prestes 580, Sao Paulo 05508-080, SP, Brazil.
FAU - Duque, Marcelo Dutra
AU  - Duque MD
AUID- ORCID: 0000-0002-4080-9862
AD  - Department of Pharmaceutical Sciences, Institute of Environmental, Chemical and 
      Pharmaceutical Sciences, Universidade Federal de Sao Paulo-UNIFESP, Rua Sao 
      Nicolau, 210 Centro, Diadema 09913-030, SP, Brazil.
FAU - Ferraz, Humberto Gomes
AU  - Ferraz HG
AD  - Department of Pharmacy, Faculty of Pharmaceutical Sciences, Universidade de Sao 
      Paulo-USP, Av. Prof. Lineu Prestes 580, Sao Paulo 05508-080, SP, Brazil.
LA  - eng
GR  - Finance Code 001/Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior/
GR  - Process number 159346/2015-0/National Council for Scientific and Technological 
      Development/
PT  - Journal Article
DEP - 20220419
PL  - Switzerland
TA  - Pharmaceutics
JT  - Pharmaceutics
JID - 101534003
PMC - PMC9146084
OTO - NOTNLM
OT  - DOE
OT  - GastroPlus(R)
OT  - PBBM
OT  - bioequivalence
OT  - metoprolol succinate
OT  - mini-tablets
OT  - virtual bioequivalence study
COIS- The authors declare no conflict of interest.
EDAT- 2022/05/29 06:00
MHDA- 2022/05/29 06:01
PMCR- 2022/04/19
CRDT- 2022/05/28 01:38
PHST- 2022/03/18 00:00 [received]
PHST- 2022/04/09 00:00 [revised]
PHST- 2022/04/12 00:00 [accepted]
PHST- 2022/05/28 01:38 [entrez]
PHST- 2022/05/29 06:00 [pubmed]
PHST- 2022/05/29 06:01 [medline]
PHST- 2022/04/19 00:00 [pmc-release]
AID - pharmaceutics14050892 [pii]
AID - pharmaceutics-14-00892 [pii]
AID - 10.3390/pharmaceutics14050892 [doi]
PST - epublish
SO  - Pharmaceutics. 2022 Apr 19;14(5):892. doi: 10.3390/pharmaceutics14050892.