Category: Formulation and Quality
Purpose: Mucoadhesion provides benefits in pharmaceutical and oral care applications, enhancing drug delivery and/or providing other therapeutic advantages (local protection, lubrication, etc.).
Carbopol® polymers (carbomers) and Noveon® polycarbophil are high molecular weight polymers of acrylic acid crosslinked with polyalkenyl alcohols or divinyl glycol. When placed in contact with an aqueous medium, they hydrate and swell through hydrogen bonding or electrostatic repulsion (when neutralized). These mechanisms are the basis of the excipients’ functionality in mucoadhesion applications. Earlier studies1 showed Carbopol® polymers to have superior mucoadhesive properties when compared to other pharmaceutical excipients, such as carrageenan, xanthan, sodium CMC, methyl vinyl ether/maleic anhydride copolymer, hydroxypropyl cellulose, ethylene oxide and propylene oxide block copolymer.
The current study was designed to evaluate Carbopol® polymers and Noveon® polycarbophil for mucoadhesive properties in liquid and semisolid formulations.
Methods: Carbopol® 971P NF and 974P NF polymers and Noveon® AA-1 polycarbophil were used for the study. Typically, the polymer was dispersed at desired concentration in deionized water or anhydrous medium (glycerin/propylene glycol/PEG 400 mixture), followed by neutralization (when required). Mucoadhesive studies of the Carbopol® polymers and Noveon® polycarbophil formulations were performed using an in-house adapted in-vitro esophageal retention (IVOR) model to simulate oral/peroral conditions (Figure 1). Eluted fractions were collected up to 45 minutes and quantified by UV- Vis using a marker.
The design space for the study is presented in Figure 2.
Results: Carbopol® polymers and Noveon® polycarbophil had better mucoadhesion in neutralized vs. un-neutralized form for the same dispersion medium and concentration. The impact of concentration on the mucoadhesive properties of the studied formulations was more pronounced in the un-neutralized form. Carbopol® 971P NF polymer in aqueous systems, despite lower viscosity, showed better retention when compared to Carbopol® 974P NF polymer and Noveon® AA-1 polycarbophil. Anhydrous formulations had similar retention to the aqueous formulations at the initial time points (2 – 5 min), however they eluted much faster as time progressed.
These results support the mechanism of adhesion for Carbopol® polymers and Noveon® polycarbophil:
a. Initial contact with the mucus (wetting): The hydration potential of Carbopol® polymers and Noveon® polycarbophil allows to quickly establish contact with mucus upon application of dosage form;
b. Consolidation of adhesion: Hydrogen bonding and/or macromolecular interchain penetration between Carbopol® polymers/ Noveon® polycarbophil and components of mucin.
Within the boundaries of the general mucoadhesion mechanism, differences observed for mucoadhesion strength in liquid/semisolid formulations of Carbopol® polymers and Noveon® polycarbophil were dictated by parameters such as: degree of neutralization of the polymer, dispersion medium, and degree of crosslinking.
When the polymer is in its neutralized form, it is swollen at its largest extent and macromolecular interpenetration with the glycoprotein chains in the mucus provides strong mucoadhesion. On the other hand, in anhydrous media and in un-neutralized form the predominant mechanism is the hydrogen bonding between the carboxylic groups and the mucus components, which leads to less retention of formulation on the membrane.
Conclusion: Carbopol® polymers and Noveon® polycarbophil mucoadhesive properties in liquid and semisolid formulations were demonstrated by in-vitro IVOR studies. Longer retention of formulations was achieved with higher polymer inclusion levels and for higher degree of neutralization, irrespective of the dispersion medium.
Carbopol® polymers and Noveon® polycarbophil offer pharmaceutical scientists the flexibility to tailor properties of mucoadhesive liquid and semisolid formulations.
Liliana Miinea– Cleveland, Ohio
Liliana Miinea– Cleveland, Ohio
Paul Basone– Cleveland, Ohio
James Baxter– Cleveland, Ohio
Elena Draganoiu– Lubrizol LifeSciences, Vaughan, Ontario, Canada
Elena Draganoiu– Lubrizol, Cleveland, OH