Solute and solvent effects on the thermorheological properties of poly(oxyethylene)–poly(oxypropylene) block copolymers: Implications for pharmaceutical dosage form design

Abstract

Despite their widespread use as platforms for topical drug delivery systems, there is a relative lack of information concerning the thermorheological and viscoelastic properties of poloxamer systems and the effects of formulation components on these properties. To address this deficit, we examined the effects of the poloxamer concentration (25 and 35% w/w), molecular weight blend (poloxamer 407 and poloxamer 188), cosolvents (ethanol, propylene glycol, and glycerol), and presence of inorganic and organic electrolytes (sodium chloride and tetracaine hydrochloride, respectively) on these properties. The rheological properties were examined with a rheometer (4-cmdiameter, stainless steel, parallel-plate geometry) in either thermal sweep (0.5 Hz) or frequency sweep (0.01-1.0 Hz and 37°C) modes. Increasing the poloxamer concentration increased the elasticity [i.e., increased the storage modulus (GЈ) and reduced the loss tangent (tan ␦)] and reduced the sol-gel transition temperature (T m ) of all the formulations. Decreasing the ratio (407:188) increased T m and reduced the elasticity of all the formulations. Increasing the concentration of ethanol, propylene glycol, or glycerol in the solvent reduced T m . The presence of ethanol reduced GЈ and increased tan ␦ in a concentration-dependent fashion, whereas the viscoelastic properties of the poloxamers were more tolerant of glycerol (in particular) and propylene glycol. The elasticity of the formulations containing up to 10% glycerol and 5% propylene glycol was increased with respect to their aqueous counterparts. The presence of sodium chloride reduced T m and, at lower concentrations (1 and 3%), increased GЈ and reduced tan ␦ for aqueous poloxamer systems. Conversely, the addition of a model therapeutic agent, tetracaine hydrochloride (5 and 7% w/w), significantly increased T m and altered the viscoelastic character of the poloxamer system, notably reducing GЈ and increasing the loss modulus and tan ␦. Alterations in the viscoelastic and thermorheological properties of aqueous poloxamer systems will have implications for their clinical performance. This study, therefore, has highlighted the need for the rational selection of components in the formulation of poloxamer systems as platforms for topical drug delivery.

Novel semi-interpenetrating hydrogel networks with enhanced mechanical properties and thermoresponsive engineered drug delivery, designed as bioactive endotracheal tube biomaterials

“…Whilst other polymeric candidates have been examined as platforms for thermoresponsive drug delivery, e.g. poloxamers [35,36], the majority of thermoresponsive drug delivery platforms have involved poly(NIPAA) or copolymers of this monomer with other acrylate monomers [37][38][39][40][41]. Although the ability to poly(NIPAA)-based polymers to offer stimuli sensitive release has been recognised, one of the main limitations associated with the use of these systems as bioactive implants is their sub-optimal mechanical properties [23,42].…”

Effect of ethanol on the gelation of aqueous solutions of Pluronic F127

“…These studies [5,6] have indicated that the critical gel concentration at a given temperature (cgc) and the critical gel temperature at a given concentration (cgt) are increased by addition of ethanol. Jones et al [8] have reported the opposite effect, i.e. a decrease in the cgt of 25 wt.% F127 gels as the proportion of ethanol in the solvent is increased in the range 0-20 wt.%, possibly reflecting their different derivation of the cgt from the temperature dependence of elastic modulus.…”

Synthesis, rheological behavior and swelling properties of copolymer hydrogels based on poly(N-isopropylacrylamide) with hydrophilic monomers

“…Instruments) under the oscillatory shear. The flow of dilute hydrogel suspensions under shear was studied in Couette geometry, using a pair of coaxial cylinders with 15 mm of external diameter and gap of 1 mm [23]. Silicone oil was added to the surface of the sample to prevent evaporation during measurements.…”

“…The miscible hydrogel would exhibit a single transition between T g of the two components. The glass transition temperature of linear poly (N-isopropylacrylamide) homopolymer is between 85 and 130 °C, probably depending on molecular weight [23]. In Figure 3(a), a relaxation endotherm at 122 °C identifies the glass transition temperature observed for the PNIPAAm [26].…”