TY - JOUR
T1 - Specific interactions between diphenhydramine and α-helical poly(glutamic acid) - A new ion-pairing complex for taste masking and pH-controlled diphenhydramine release
AU - Agresti, Ciara
AU - Tu, Zhigang
AU - Ng, Charlene
AU - Yang, Yongsheng
AU - Liang, Jun F.
PY - 2008/9
Y1 - 2008/9
N2 - Formation of drug/excipient complex through ionic interactions has proven to be very effective for both controlled release and taste masking. Unfortunately, the ionic interactions between drugs and small molecule excipients are usually weak, and the stability of the formed complexes can be greatly influenced by solution ionic strength. In this study, we explored to formulate diphenhydramine (DPH), a very bitter tasting drug, using small molecular weight and carboxyl group containing polymers. Studies showed that DPH interacted with α-helical poly(glutamic acid) specifically to produce DPH/poly(glutamic acid) complexes, mostly spherical in shape with a diameter of around 1.0 μm. Other drugs with similar chemical structures as DPH, such as phenylephrine and pseudoephedrine, could not form complexes with poly(glutamic acid) or other polymers under the same conditions. Although DPH in DPH/poly(glutamic acid) complexes existed amorphously, it showed increased stability.In vitro studies using electronic tongue demonstrated that poly(glutamic acid) might be as effective as sucralose for DPH bitter taste blocking. In addition, DPH/poly(glutamic acid) complexes were not stable in neutral or weak acidic (pH > 5) environments and dissolved rapidly and completely. Therefore, DPH/poly(glutamic acid) complex may serve as a new formulation for taste masking and controlled DPH release in gastrointestinal tract. This is the first report that small molecule drugs can interact with peptides of specific secondary structures to form stable complexes. In addition to greatly expanded ion-pairing excipient pool, application of peptides in drug formulation may also solve the selectivity and stability problems faced by current small molecule excipients.
AB - Formation of drug/excipient complex through ionic interactions has proven to be very effective for both controlled release and taste masking. Unfortunately, the ionic interactions between drugs and small molecule excipients are usually weak, and the stability of the formed complexes can be greatly influenced by solution ionic strength. In this study, we explored to formulate diphenhydramine (DPH), a very bitter tasting drug, using small molecular weight and carboxyl group containing polymers. Studies showed that DPH interacted with α-helical poly(glutamic acid) specifically to produce DPH/poly(glutamic acid) complexes, mostly spherical in shape with a diameter of around 1.0 μm. Other drugs with similar chemical structures as DPH, such as phenylephrine and pseudoephedrine, could not form complexes with poly(glutamic acid) or other polymers under the same conditions. Although DPH in DPH/poly(glutamic acid) complexes existed amorphously, it showed increased stability.In vitro studies using electronic tongue demonstrated that poly(glutamic acid) might be as effective as sucralose for DPH bitter taste blocking. In addition, DPH/poly(glutamic acid) complexes were not stable in neutral or weak acidic (pH > 5) environments and dissolved rapidly and completely. Therefore, DPH/poly(glutamic acid) complex may serve as a new formulation for taste masking and controlled DPH release in gastrointestinal tract. This is the first report that small molecule drugs can interact with peptides of specific secondary structures to form stable complexes. In addition to greatly expanded ion-pairing excipient pool, application of peptides in drug formulation may also solve the selectivity and stability problems faced by current small molecule excipients.
KW - Controlled release
KW - Formulation
KW - Nanoparticles
KW - Peptide
KW - Taste masking
KW - pH-sensitivity
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U2 - 10.1016/j.ejpb.2008.04.004
DO - 10.1016/j.ejpb.2008.04.004
M3 - Article
C2 - 18514496
AN - SCOPUS:50149097237
SN - 0939-6411
VL - 70
SP - 226
EP - 233
JO - European Journal of Pharmaceutics and Biopharmaceutics
JF - European Journal of Pharmaceutics and Biopharmaceutics
IS - 1
ER -