PMID- 38056285
OWN - NLM
STAT- MEDLINE
DCOM- 20240105
LR  - 20240105
IS  - 1873-264X (Electronic)
IS  - 0731-7085 (Linking)
VI  - 239
DP  - 2024 Feb 15
TI  - Leveraging ToF-SIMS imaging to investigate tenofovir disoproxil fumarate 
      degradation at excipient interfaces in oral compressed tablets.
PG  - 115863
LID - S0731-7085(23)00632-5 [pii]
LID - 10.1016/j.jpba.2023.115863 [doi]
AB  - Time-of-flight secondary ion mass spectrometry (ToF-SIMS) imaging has been used 
      to study the hydrolysis of tenofovir disoproxil fumarate (TDF) to tenofovir 
      monosoproxil (TM) within an oral compressed tablet. The ToF-SIMS images displayed 
      a heterogenous distribution of the matrix components. Evaluation of the TM 
      distribution revealed that it was primarily co-localized with areas of higher 
      excipient concentration pointing toward excipient driven degradation. To support 
      these observations, a compatibility study of TDF with each tablet component was 
      performed via liquid chromatography. The ToF-SIMS imaging and compatibility study 
      indicated that the excipient, Avicel(R) PH-102, was the primary driver of TM 
      formation in the tablet. The hydrolysis degradation mechanism within the tablet 
      is further rationalized through discussion of chemical and physical properties of 
      the matrix components. The sum of this work demonstrates a new analytical 
      workflow for probing and understanding matrix driven degradation in oral 
      compressed tablets utilizing ToF-SIMS imaging.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Topolski, Josey E
AU  - Topolski JE
AD  - Merck & Co., Inc., 126 E. Lincoln Ave Rahway, NJ 07065, USA. Electronic address: 
      josey.topolski@merck.com.
FAU - Sheng, Huaming
AU  - Sheng H
AD  - Merck & Co., Inc., 126 E. Lincoln Ave Rahway, NJ 07065, USA.
FAU - Moore, Colman
AU  - Moore C
AD  - Merck & Co., Inc., 126 E. Lincoln Ave Rahway, NJ 07065, USA.
FAU - Rading, Derk
AU  - Rading D
AD  - IONTOF Technologies GmbH, Heisenbergstrasse 15, 48149 Munster, Germany.
FAU - Moyer, Tessa B
AU  - Moyer TB
AD  - Merck & Co., Inc., 126 E. Lincoln Ave Rahway, NJ 07065, USA.
FAU - Punia, Ashish
AU  - Punia A
AD  - Merck & Co., Inc., 126 E. Lincoln Ave Rahway, NJ 07065, USA.
FAU - Lamm, Matthew S
AU  - Lamm MS
AD  - Merck & Co., Inc., 126 E. Lincoln Ave Rahway, NJ 07065, USA.
FAU - Pierson, Elizabeth
AU  - Pierson E
AD  - Merck & Co., Inc., 126 E. Lincoln Ave Rahway, NJ 07065, USA.
LA  - eng
PT  - Journal Article
DEP - 20231119
PL  - England
TA  - J Pharm Biomed Anal
JT  - Journal of pharmaceutical and biomedical analysis
JID - 8309336
RN  - 99YXE507IL (Tenofovir)
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Excipients)
RN  - 0 (Tablets)
SB  - IM
MH  - Humans
MH  - Tenofovir/therapeutic use
MH  - *Anti-HIV Agents/therapeutic use
MH  - Excipients/chemistry
MH  - Spectrometry, Mass, Secondary Ion
MH  - Tablets/chemistry
MH  - *HIV Infections/drug therapy
OTO - NOTNLM
OT  - API-excipient interactions
OT  - Degradation
OT  - Mass spectrometry imaging
OT  - Oral compressed tablets
OT  - Tenofovir disoproxil fumarate
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/12/07 00:42
MHDA- 2024/01/05 06:42
CRDT- 2023/12/06 18:12
PHST- 2023/09/19 00:00 [received]
PHST- 2023/11/15 00:00 [revised]
PHST- 2023/11/15 00:00 [accepted]
PHST- 2024/01/05 06:42 [medline]
PHST- 2023/12/07 00:42 [pubmed]
PHST- 2023/12/06 18:12 [entrez]
AID - S0731-7085(23)00632-5 [pii]
AID - 10.1016/j.jpba.2023.115863 [doi]
PST - ppublish
SO  - J Pharm Biomed Anal. 2024 Feb 15;239:115863. doi: 10.1016/j.jpba.2023.115863. 
      Epub 2023 Nov 19.