PMID- 30362772
OWN - NLM
STAT- MEDLINE
DCOM- 20190909
LR  - 20190909
IS  - 1543-8392 (Electronic)
IS  - 1543-8384 (Linking)
VI  - 15
IP  - 12
DP  - 2018 Dec 3
TI  - In Situ Stimulated Raman Scattering (SRS) Microscopy Study of the Dissolution of 
      Sustained-Release Implant Formulation.
PG  - 5793-5801
LID - 10.1021/acs.molpharmaceut.8b00965 [doi]
AB  - Localized drug delivery systems (DDSs) provide therapeutic levels of drug agent 
      while mitigating side effects of systemic delivery. These systems offer 
      controlled release over extended periods of time making them attractive 
      therapies. Monitoring drug dissolution is vital for developing safe and effective 
      means of drug delivery. Currently, dissolution characterization methods are 
      limited to bulk analysis and cannot provide dissolution kinetics at high spatial 
      resolution. However, dissolution rates of drug particles can be heterogeneous 
      with influences from many factors. Insights into finer spatiotemporal dynamics of 
      single particle dissolution could potentially improve pharmacokinetic modeling of 
      dissolution for future drug development. In this work, we demonstrate 
      high-resolution chemical mapping of entecavir, a hepatitis B antiviral drug, 
      embedded in a slow release poly(d,l-lactic acid) formulation with stimulated 
      Raman scattering (SRS) microscopy. By tracking the volume change of individual 
      micron-sized drug particles within the polymer matrix, we establish an analytical 
      protocol for quantitatively profiling dissolution of single crystalline particles 
      in implant formulations in an in situ manner.
FAU - Francis, Andrew T
AU  - Francis AT
AUID- ORCID: 0000-0003-3192-5260
AD  - Department of Chemistry , University of Washington , Seattle , Washington 98195 , 
      United States.
FAU - Nguyen, Tai T
AU  - Nguyen TT
AD  - Department of Chemistry , University of Washington , Seattle , Washington 98195 , 
      United States.
FAU - Lamm, Matthew S
AU  - Lamm MS
AD  - MRL, Merck & Co., Inc. , Kenilworth , New Jersey 07033 , United States.
FAU - Teller, Ryan
AU  - Teller R
AD  - MRL, Merck & Co., Inc. , Kenilworth , New Jersey 07033 , United States.
FAU - Forster, Seth P
AU  - Forster SP
AD  - MRL, Merck & Co., Inc. , Kenilworth , New Jersey 07033 , United States.
FAU - Xu, Wei
AU  - Xu W
AD  - MRL, Merck & Co., Inc. , Kenilworth , New Jersey 07033 , United States.
FAU - Rhodes, Timothy
AU  - Rhodes T
AD  - MRL, Merck & Co., Inc. , Kenilworth , New Jersey 07033 , United States.
FAU - Smith, Ronald L
AU  - Smith RL
AD  - MRL, Merck & Co., Inc. , Kenilworth , New Jersey 07033 , United States.
FAU - Kuiper, Jesse
AU  - Kuiper J
AD  - MRL, Merck & Co., Inc. , Kenilworth , New Jersey 07033 , United States.
FAU - Su, Yongchao
AU  - Su Y
AUID- ORCID: 0000-0001-5063-3218
AD  - MRL, Merck & Co., Inc. , Kenilworth , New Jersey 07033 , United States.
FAU - Fu, Dan
AU  - Fu D
AUID- ORCID: 0000-0001-9243-8306
AD  - Department of Chemistry , University of Washington , Seattle , Washington 98195 , 
      United States.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181108
PL  - United States
TA  - Mol Pharm
JT  - Molecular pharmaceutics
JID - 101197791
RN  - 0 (Drug Carriers)
RN  - 0 (Drug Implants)
RN  - 0 (Polyesters)
RN  - 459TN2L5F5 (poly(lactide))
RN  - 5968Y6H45M (entecavir)
RN  - 5Z93L87A1R (Guanine)
SB  - IM
MH  - Chemistry, Pharmaceutical/methods
MH  - Drug Carriers/*chemistry
MH  - Drug Implants/administration & dosage/*pharmacokinetics
MH  - *Drug Liberation
MH  - Guanine/administration & dosage/*analogs & derivatives/pharmacokinetics
MH  - Microscopy/methods
MH  - Particle Size
MH  - Polyesters/chemistry
MH  - Spectrum Analysis, Raman/methods
OTO - NOTNLM
OT  - drug delivery systems
OT  - in situ particle dissolution
OT  - nonlinear spectroscopy
OT  - optical imaging
OT  - stimulated Raman scattering
EDAT- 2018/10/27 06:00
MHDA- 2019/09/10 06:00
CRDT- 2018/10/27 06:00
PHST- 2018/10/27 06:00 [pubmed]
PHST- 2019/09/10 06:00 [medline]
PHST- 2018/10/27 06:00 [entrez]
AID - 10.1021/acs.molpharmaceut.8b00965 [doi]
PST - ppublish
SO  - Mol Pharm. 2018 Dec 3;15(12):5793-5801. doi: 10.1021/acs.molpharmaceut.8b00965. 
      Epub 2018 Nov 8.