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Zero-order release formulations using a novel cellulose ester

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Abstract

New carboxymethylcellulose esters were developed with useful properties for oral dosage forms in drug delivery. Normally, commercial cellulose esters are used as the major excipients in oral dosage forms as a coating or a membrane. In applications involving compression tablets, cellulose esters are usually mixed with other more hydrophilic matrix components to facilitate dissolution of the active. In the present study, novel cellulose esters were single component matrix resins. Pharmaceutical actives were cryogenically ground as a physical blend or an amorphous blend with the polymer. Subsequently, tablets were made by direct compression using a single tablet press, or capsules were made by filling them with the ground material. Dissolution tests were completed on the solid dosage forms at pH 1.2, 4.5, 6.8 or 7.4 in a United States Pharmacopeia (USP) II device to determine the release profiles for up to 24 h. Carboxymethylcellulose esters provide an excellent matrix for controlling both the rate of release and the pH at which pharmaceutical actives release into the aqueous environment. When used in suitable quantities, dictated by the active of interest, carboxymethylcellulose acetate butyrate provided zero-order release over sustained time up to 24 h.

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Abbreviations

Ac:

Acetyl

BCS:

Biopharmaceutics Classification System

Bu:

Butyryl

CA:

Cellulose Acetate

CAB:

Cellulose acetate butyrate

CM:

Carboxymethyl

CMCA:

Carboxymethylcellulose acetate

CMCAB:

Carboxymethylcellulose acetate butyrate

CMCAP:

Carboxymethylcellulose acetate propionate

CMC:

Carboxymethylcellulose

DS:

Degree of substitution

Eastman EB:

Ethylene glycol monobutyl ether

MC:

microcrystalline cellulose

Na-CMC:

Sodium carboxymethylcellulose

NF:

National Formulary

rpm:

revolutions per minute

PEO:

polyethylene oxide

Pr:

Propionyl

TEC:

triethyl citrate

Tg:

glass transition temperature

USP:

United States Pharmacopeia

WHO:

World Health Organization

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Authors and Affiliations

  1. Eastman Chemical Company Research Laboratories, 1972, Kingsport, Tennessee, 37662-5150, USA

    Jessica D. Posey-Dowty, Thelma L. Watterson, A. Kent Wilson, Kevin J. Edgar, Michael C. Shelton & Larry R. Lingerfelt Jr.

Authors
  1. Jessica D. Posey-Dowty
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  2. Thelma L. Watterson
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  3. A. Kent Wilson
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  4. Kevin J. Edgar
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  5. Michael C. Shelton
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  6. Larry R. Lingerfelt Jr.
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Corresponding author

Correspondence to Jessica D. Posey-Dowty.

Appendix

Appendix

Table 3. Weight change of CMCAB films as a func„tion of pH.
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Posey-Dowty, J.D., Watterson, T.L., Wilson, A.K. et al. Zero-order release formulations using a novel cellulose ester. Cellulose 14, 73–83 (2007). https://doi.org/10.1007/s10570-006-9079-7

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  • DOI: https://doi.org/10.1007/s10570-006-9079-7

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