Category: Formulation and Quality
Purpose: Carbomers are cross-linked polymers of acrylic acid that are commonly used as excipients in the formulation of semi-solid and solid dosage forms. They are used as thickeners, emulsifiers and emulsion bases in topical dosage forms as well as matrix forming agents in solid dosage forms. Carbomers are commercially available in various grades differing in their crosslinks, crosslinking densities and the amount of added hydrophobic monomers in the poly(acrylic acid) structure. Similarly, polycarbophil is also a high molecular weight cross-linked poly(acrylic acid) used as a controlled release agent in tablets as well as a bioadhesive excipient in buccal, vaginal, and ophthalmic dosage forms.
The objective of our study was to evaluate the effect of crosslinker type and crosslinking density on the flow behavior of carbomers and polycarbophil at different solution concentrations. We examined three different types of crosslinked poly(acrylic acid)s including two homopolymers of acrylic acid crosslinked with allyl sucrose or allyl pentaerythritol possessing different crosslinking densities and polycarbophil, a poly(acrylic acid) homopolymer crosslinked with divinyl glycol. Understanding the rheological behavior of these excipients is critically important in dosage from design as it can affect the final product properties such as stability, consistency, application, and drug release.
Methods: Solutions of carbomers (carbomer homopolymer type A (Carbopol® 981) and type B (Carbopol® 974P) and polycarbophil (Noveon®) were prepared in deionized water at different concentrations (0.1-1.0% w/w) and neutralized to the pH of 5.0-6.0 using NaOH. A cone & plate rheometer (spindles 2.4 cm or 1.2 cm, 0.5 mL sample, 25°C) was used to construct the shear stress/shear rate and viscosity/shear rate rheograms at different spindle speeds. Only, the shear stresses with torque values between 10-100% were accepted.
Results: The obtained flow profiles demonstrated a pseudoplastic behavior for all the polymers at almost all concentrations. At low concentrations (0.1 and 0.3% w/w), the highly crosslinked carbomer (Type B) displayed lower shear stresses and hence lower viscosities compared to the lightly crosslinked one (Type A). However, as the concentration increased (0.5-1.0% w/w), the viscosity of the highly crosslinked carbomer increased to a greater degree (Fig. 1). The results also revealed that changing the crosslinker type of carbomer homopolymers (Types A and B) to divinyl glycol (as in polycarbophil) substantially affected its flow properties. At low solution concentration of 0.1% w/w, the polycarbophil displayed the least viscosity with a flow profile similar to Newtonian fluids. However, as the solution concentration increased to 0.3% w/w, it showed a viscosity similar to the lightly crosslinked carbomer (P > 0.05) (Fig. 2). Further increasing the solution concentration to 0.5-0.7% w/w resulted in substantially higher viscosities for polycarbophil which was comparable to that of the highly crosslinked carbomer (P > 0.05). It was only at 1.0% w/w concentration that the highly crosslinked carbomer (Type B) displayed higher viscosities than polycarbophil (Fig. 2).
Conclusion: Depending on its solution concentration, the type of crosslinker and the crosslinking density of the crosslinked acrylic acid homopolymers have a great impact on the rheological behavior of these polymers in the aqueous medium. Assuming the same backbone molecular weight for the acrylic acid homopolymers, the polycarbophil can show rheological properties similar to both lightly crosslinked and highly crosslinked homopolymers at low and high solution concentrations, respectively. Furthermore, compared to the lightly crosslinked carbomer, both highly crosslinked and polycarbophil homopolymers were shown to be more dependent on solution concentration. Our results also suggest for the highly crosslinked and polycarbophil homopolymers, a critical concentration needs to be reached before these can reasonably offer a proper performance in their dosage forms.
Hossein Omidian– Fort Lauderdale, Florida