Use of .BETA.-Cyclodextrins to Prevent Modifications of the Properties of Carbopol Hydrogels Due to Carbopol-Drug Interactions.

Abstract

Hydrogels are networks constituted by a crosslinked polymeric material that swells in water and biological fluids. The characteristics of hydrogels make them highly suited for use in controlled-release systems, whether at swelling equilibrium or as part of dynamic systems in which release and swelling occur simultaneously.1) Numerous studies have investigated the behaviour of a) hydrogels that swell in response to ambient conditions (pH, temperature, ionic strength, concentration of chemicals), 2,3) and b) of bioadhesive hydrogels. [4][5][6][7] Most such systems are constituted by hydrophilic polymers containing a large number of ionizable groups (carboxyls, hydroxyls, amines, etc.), notably metacrylic acid and polyacrylic acid derivatives.A major drawback of hydrogel-forming polymers is that they typically interact with many types of molecule, such as other polymers or low-molecular-weight molecules including certain drugs. [8][9][10] The nature of such interactions varies (ionic interaction, hydrogen bonds, etc.), depending on the characteristics of the polymer and the drug.The permeability of solutes through hydrogels depends largely on the hydrogel's internal structure, which governs its porosity, hydrophobicity, elasticity and thus swelling and release properties. When interactions arise between a hydrogelforming polymer and another component of the formulation, the properties of the formulation may be affected, with consequent effects on both its efficacy and stability. The elimination or minimization of interactions of this type is thus clearly of great practical interest.Cyclodextrins (CDs) are pharmaceutical excipients frequently used with the aim of increase in the solubility and bioavailability of poorly hydrosoluble drugs. One of the key advantages of CD inclusion compounds is that the drug is contained within the CD cavity and thus protected from the external medium. Using this approach, labile drugs have been protected against oxidation, hydrolysis and photodecomposition.11) Furthermore, the complexation of drug molecules in the apolar interior of CD inclusion compounds may induce changes in drug properties including pK a , spectroscopic properties (visible/UV absorption, IR absorption, or fluorescence) and chemical properties (notably reactivity).In the present study we investigated interactions between three varieties of Carbopol ® (a carbomer that is widely used in the manufacture of pharmaceutical gels and bioadhesive hydrogels) and propranolol hydrochloride (PRP, a cationic drug). The Carbopols are high-molecular-weight carboxyvinylic derivatives comprising polyacrylic acid subunits crosslinked with allyl saccharose or pentaerithritol allyl ethers. PRP is known to interact with polyacrylic acid, 10) and to form stable inclusion compounds with CDs (binding constant of 220Ϯ20 M Ϫ1 at pH 7 calculated using liquid chromatography method).12) We investigated the effects of carbomer/drug interactions on the principal characteristics of the system, namely drug solubility, swelling, drug release and bi...

A vaginal drug delivery model

“…Carbopol has been reported to interact strongly with low molecular weight drugs and cause precipitation (Blanco-Fuente et al, 2002). But in our case, physicochemical status of drug or SLN does not affect gelling temperature significantly.…”

Affinity‐Based Drug Delivery

“…TA is hydrophobic and does not interact with carboxylic acid groups, [112] whereas propranolol is a fairly soluble drug that strongly interacts with acrylic networks. [113,114] Hydrogels with CD moieties present showed extended release of TA when compared with hydrogels with no CD, indicating affinity of TA with the CD cavities control release of the hydrophobic drug. For propranolol, no clear relationship between the release rate and proportion of g-CD-NMA in the network was determined, indicating release was not strongly governed by interaction with CD moieties.…”

Improvements in Topical Ocular Drug Delivery Systems: Hydrogels and Contact Lenses

“…The incorporation of additives into hydrogels can change the viscosity of the microenvironment and/or its polarity, changing the distribution of drugs and modulating their release. These effects are more remarkable when the additive interacts with the drug or the polymer chains, altering the drug-hydrogel interactions (26,27). As a result, hydrogels are commonly used in clinical practice and experimental medicine for wide range applications, including diagnostics, coating, molecular immobilization, tissue engineering, cells separation, scaffolds, design and production of devices as contact lenses.…”