PMID- 34481906
OWN - NLM
STAT- MEDLINE
DCOM- 20220127
LR  - 20220127
IS  - 1873-3441 (Electronic)
IS  - 0939-6411 (Linking)
VI  - 168
DP  - 2021 Nov
TI  - Design of ultra-fine carvedilol nanococrystals: Development of a safe and stable 
      injectable formulation.
PG  - 139-151
LID - S0939-6411(21)00227-7 [pii]
LID - 10.1016/j.ejpb.2021.08.015 [doi]
AB  - Carvedilol (CAR) is a strategic beta-blocker agent which its application has been 
      limited by its very low water solubility. The present study describes a soluble 
      form of drug based on nano-cocrystal (NCC) anti-solvent precipitation technique. 
      The COSMOquick software was employed to select the optimum coformer (tartaric 
      acid, TA) and organic solvent (acetone) relying on the enthalpy changes of 
      cocrystallization and solubilization. Central Composite Design (CCD) considering 
      the impact of CAR, TA, poloxamer 188 (stabilizer) concentrations, and 
      anti-solvent/solvent ratio on CAR NCCs particle size (PS) could produce 
      ultra-fine NCCs (about 1 nm). The lyophilization of NCCs investigating slow/fast 
      freezing rates, various types and concentrations of cryprotectants and 
      lyoprotectants indicated that PEG and trehalose (5 % w/vconcentration) under slow 
      freezing rate could re-produce the initial PSs successfully. CAR NCCs indicated 
      about 2000 fold increase in solubility compared with pure CAR. DSC and PXRD 
      experiments proved that the formulations containing trehalose led to more 
      crystalline and the ones comprising PEG led to more amorphous structures. 
      Interestingly, the slow freezed PEG protected NCCs were physically stable for at 
      least 18 months. In conclusion, the NCC technology could produce the first safe 
      soluble form of CAR for treating hypertension urgencies easy for industrial 
      scale-up.
CI  - Copyright (c) 2021 Elsevier B.V. All rights reserved.
FAU - Mohammady, Mohsen
AU  - Mohammady M
AD  - Department of Pharmaceutics, School of Pharmacy, Shiraz University of Medical 
      Sciences, Shiraz, Iran.
FAU - Hadidi, Mohammad
AU  - Hadidi M
AD  - Department of Pharmaceutics, School of Pharmacy, Shiraz University of Medical 
      Sciences, Shiraz, Iran.
FAU - Iman Ghetmiri, Seyed
AU  - Iman Ghetmiri S
AD  - Department of Pharmaceutics, School of Pharmacy, Shiraz University of Medical 
      Sciences, Shiraz, Iran.
FAU - Yousefi, Gholamhossein
AU  - Yousefi G
AD  - Department of Pharmaceutics, School of Pharmacy, Shiraz University of Medical 
      Sciences, Shiraz, Iran; Center for Nanotechnology in Drug Delivery, Shiraz 
      University of Medical Sciences, Shiraz, Iran. Electronic address: 
      ghyousefi@sums.ac.ir.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20210902
PL  - Netherlands
TA  - Eur J Pharm Biopharm
JT  - European journal of pharmaceutics and biopharmaceutics : official journal of 
      Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
JID - 9109778
RN  - 0 (Adrenergic beta-Antagonists)
RN  - 0 (Excipients)
RN  - 0 (Solvents)
RN  - 0K47UL67F2 (Carvedilol)
RN  - B8WCK70T7I (Trehalose)
SB  - IM
MH  - Adrenergic beta-Antagonists/*administration & dosage/chemistry
MH  - Carvedilol/*administration & dosage/chemistry
MH  - Chemistry, Pharmaceutical/methods
MH  - Crystallization
MH  - Drug Design
MH  - Drug Stability
MH  - Drug Storage
MH  - Excipients/*chemistry
MH  - Freeze Drying
MH  - *Nanoparticles
MH  - Particle Size
MH  - Solubility
MH  - Solvents/chemistry
MH  - Time Factors
MH  - Trehalose/chemistry
OTO - NOTNLM
OT  - Carvedilol
OT  - Coformer
OT  - Hypertension crises
OT  - Injectable
OT  - Nano-cocrystal
OT  - Ultra-fine
EDAT- 2021/09/06 06:00
MHDA- 2022/01/28 06:00
CRDT- 2021/09/05 20:37
PHST- 2021/05/26 00:00 [received]
PHST- 2021/07/18 00:00 [revised]
PHST- 2021/08/25 00:00 [accepted]
PHST- 2021/09/06 06:00 [pubmed]
PHST- 2022/01/28 06:00 [medline]
PHST- 2021/09/05 20:37 [entrez]
AID - S0939-6411(21)00227-7 [pii]
AID - 10.1016/j.ejpb.2021.08.015 [doi]
PST - ppublish
SO  - Eur J Pharm Biopharm. 2021 Nov;168:139-151. doi: 10.1016/j.ejpb.2021.08.015. Epub 
      2021 Sep 2.