Effect of stabilizer on the maximum degree and extent of supersaturation and oral absorption of tacrolimus made by ultra-rapid freezing

Kirk A. Overhoff; Jason T. McConville; Wei Yang; Keith P. Johnston; Jay I. Peters; Robert O. Williams

doi:10.1007/s11095-007-9417-y

Effect of stabilizer on the maximum degree and extent of supersaturation and oral absorption of tacrolimus made by ultra-rapid freezing

Kirk A. Overhoff, Jason T. McConville, Wei Yang, Keith P. Johnston, Jay I. Peters, Robert O. Williams

Department of Medicine

Research output: Contribution to journal › Article › peer-review

95 Scopus citations

Abstract

Purpose. Solid dispersions containing various stabilizers and tacrolimus (TAC) prepared by an Ultra-rapid Freezing (URF) process were investigated to determine the effect on their ability to form supersaturated solutions in aqueous media and on enhancing transport across biological membranes. Materials and Methods. The stabilizers included poly(vinyl alcohol; PVA), poloxamer 407 (P407), and sodium dodecyl sulfate (SDS). In vivo absorption enhancement in rats was also investigated. Dissolution studies were conducted at supersaturated conditions in both acidic media for 24 h and at delayed release (enteric) conditions to simulate intestinal transit. Results. The rank order of C/Ceq _max in the dissolution studies at acidic conditions was URF-P407>URF-SDS>Prograf® (PRO)>URF-PVA:P407. For C/Ceq _max under enteric conditions, the order was URF-SDS>PRO>URF- PVA:P407>URF-P407, and for the extent of supersaturation (AUC) in acidic and pH shift conditions it was URF-SDS>PRO>URF-PVA:P407>URF-P407. The pharmacokinetic data suggests URF-P407 had the greatest absorption having higher C _max with a 1.5-fold increase in AUC compared to PRO. All URF compositions had a shorter T _max compared to PRO. Conclusions. The nanostructured powders containing various stabilizing polymers formed by the URF process offer enhanced supersaturation characteristics leading to increased oral absorption of TAC.

Original language	English (US)
Pages (from-to)	167-175
Number of pages	9
Journal	Pharmaceutical Research
Volume	25
Issue number	1
DOIs	https://doi.org/10.1007/s11095-007-9417-y
State	Published - Jan 2008

Keywords

Amorphous
In vitro-in vivo correlation
Nanoparticle
Particle engineering
Rapid freezing
Supersaturation
Tacrolimus

ASJC Scopus subject areas

Biotechnology
Molecular Medicine
Pharmacology
Pharmaceutical Science
Organic Chemistry
Pharmacology (medical)

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10.1007/s11095-007-9417-y

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@article{b50945b8939d429ba0f0890b197f3ed9,

title = "Effect of stabilizer on the maximum degree and extent of supersaturation and oral absorption of tacrolimus made by ultra-rapid freezing",

abstract = "Purpose. Solid dispersions containing various stabilizers and tacrolimus (TAC) prepared by an Ultra-rapid Freezing (URF) process were investigated to determine the effect on their ability to form supersaturated solutions in aqueous media and on enhancing transport across biological membranes. Materials and Methods. The stabilizers included poly(vinyl alcohol; PVA), poloxamer 407 (P407), and sodium dodecyl sulfate (SDS). In vivo absorption enhancement in rats was also investigated. Dissolution studies were conducted at supersaturated conditions in both acidic media for 24 h and at delayed release (enteric) conditions to simulate intestinal transit. Results. The rank order of C/Ceq max in the dissolution studies at acidic conditions was URF-P407>URF-SDS>Prograf{\textregistered} (PRO)>URF-PVA:P407. For C/Ceq max under enteric conditions, the order was URF-SDS>PRO>URF- PVA:P407>URF-P407, and for the extent of supersaturation (AUC) in acidic and pH shift conditions it was URF-SDS>PRO>URF-PVA:P407>URF-P407. The pharmacokinetic data suggests URF-P407 had the greatest absorption having higher C max with a 1.5-fold increase in AUC compared to PRO. All URF compositions had a shorter T max compared to PRO. Conclusions. The nanostructured powders containing various stabilizing polymers formed by the URF process offer enhanced supersaturation characteristics leading to increased oral absorption of TAC.",

keywords = "Amorphous, In vitro-in vivo correlation, Nanoparticle, Particle engineering, Rapid freezing, Supersaturation, Tacrolimus",

author = "Overhoff, {Kirk A.} and McConville, {Jason T.} and Wei Yang and Johnston, {Keith P.} and Peters, {Jay I.} and Williams, {Robert O.}",

note = "Funding Information: The authors kindly acknowledge the financial support from The Dow Chemical Company. Kirk A. Overhoff is a continuing American Fellowship for Pharmaceutical Education (AFPE) Fellow from 2004 to 2006 and a 2005–2006 University Continuing Fellowship recipient. In addition, the authors would like to gratefully thank Dr. Nathan Wiederhold at the University of Texas Health Science Center for lending his expertise regarding the ELISA analysis.",

year = "2008",

month = jan,

doi = "10.1007/s11095-007-9417-y",

language = "English (US)",

volume = "25",

pages = "167--175",

journal = "Pharmaceutical Research",

issn = "0724-8741",

publisher = "Springer",

number = "1",

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TY - JOUR

T1 - Effect of stabilizer on the maximum degree and extent of supersaturation and oral absorption of tacrolimus made by ultra-rapid freezing

AU - Overhoff, Kirk A.

AU - McConville, Jason T.

AU - Yang, Wei

AU - Johnston, Keith P.

AU - Peters, Jay I.

AU - Williams, Robert O.

N1 - Funding Information: The authors kindly acknowledge the financial support from The Dow Chemical Company. Kirk A. Overhoff is a continuing American Fellowship for Pharmaceutical Education (AFPE) Fellow from 2004 to 2006 and a 2005–2006 University Continuing Fellowship recipient. In addition, the authors would like to gratefully thank Dr. Nathan Wiederhold at the University of Texas Health Science Center for lending his expertise regarding the ELISA analysis.

PY - 2008/1

Y1 - 2008/1

N2 - Purpose. Solid dispersions containing various stabilizers and tacrolimus (TAC) prepared by an Ultra-rapid Freezing (URF) process were investigated to determine the effect on their ability to form supersaturated solutions in aqueous media and on enhancing transport across biological membranes. Materials and Methods. The stabilizers included poly(vinyl alcohol; PVA), poloxamer 407 (P407), and sodium dodecyl sulfate (SDS). In vivo absorption enhancement in rats was also investigated. Dissolution studies were conducted at supersaturated conditions in both acidic media for 24 h and at delayed release (enteric) conditions to simulate intestinal transit. Results. The rank order of C/Ceq max in the dissolution studies at acidic conditions was URF-P407>URF-SDS>Prograf® (PRO)>URF-PVA:P407. For C/Ceq max under enteric conditions, the order was URF-SDS>PRO>URF- PVA:P407>URF-P407, and for the extent of supersaturation (AUC) in acidic and pH shift conditions it was URF-SDS>PRO>URF-PVA:P407>URF-P407. The pharmacokinetic data suggests URF-P407 had the greatest absorption having higher C max with a 1.5-fold increase in AUC compared to PRO. All URF compositions had a shorter T max compared to PRO. Conclusions. The nanostructured powders containing various stabilizing polymers formed by the URF process offer enhanced supersaturation characteristics leading to increased oral absorption of TAC.

AB - Purpose. Solid dispersions containing various stabilizers and tacrolimus (TAC) prepared by an Ultra-rapid Freezing (URF) process were investigated to determine the effect on their ability to form supersaturated solutions in aqueous media and on enhancing transport across biological membranes. Materials and Methods. The stabilizers included poly(vinyl alcohol; PVA), poloxamer 407 (P407), and sodium dodecyl sulfate (SDS). In vivo absorption enhancement in rats was also investigated. Dissolution studies were conducted at supersaturated conditions in both acidic media for 24 h and at delayed release (enteric) conditions to simulate intestinal transit. Results. The rank order of C/Ceq max in the dissolution studies at acidic conditions was URF-P407>URF-SDS>Prograf® (PRO)>URF-PVA:P407. For C/Ceq max under enteric conditions, the order was URF-SDS>PRO>URF- PVA:P407>URF-P407, and for the extent of supersaturation (AUC) in acidic and pH shift conditions it was URF-SDS>PRO>URF-PVA:P407>URF-P407. The pharmacokinetic data suggests URF-P407 had the greatest absorption having higher C max with a 1.5-fold increase in AUC compared to PRO. All URF compositions had a shorter T max compared to PRO. Conclusions. The nanostructured powders containing various stabilizing polymers formed by the URF process offer enhanced supersaturation characteristics leading to increased oral absorption of TAC.

KW - Amorphous

KW - In vitro-in vivo correlation

KW - Nanoparticle

KW - Particle engineering

KW - Rapid freezing

KW - Supersaturation

KW - Tacrolimus

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U2 - 10.1007/s11095-007-9417-y

DO - 10.1007/s11095-007-9417-y

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C2 - 17968635

AN - SCOPUS:38049112810

SN - 0724-8741

VL - 25

SP - 167

EP - 175

JO - Pharmaceutical Research

JF - Pharmaceutical Research

IS - 1

ER -

Effect of stabilizer on the maximum degree and extent of supersaturation and oral absorption of tacrolimus made by ultra-rapid freezing

Abstract

Keywords

ASJC Scopus subject areas

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