Aqueous Hydroxypropyl Research Articles

Influence of aqueous coatings on the stability of enteric coated pellets and tablets

Pancreatin pellets, placebo pellets and tablets containing vitamin B 2 were coated with various aqueous and organic enteric polymers, HPMCAS, HP, Eudragit® L 100-55, Eudragit® L 30 D-55, CAP, CAT, CMEC and PVAP, comparatively investigated and tested for storage stability. With the exception of Eudragit® L 100-55 and Eudragit® L 30 D-55, higher amounts of coating material were needed to achieve gastro-resistance with aqueous coating than with organic coating. Film formation from aqueous dispersions of micronized HP 55 was affected by the degree of micronization and was improved by reducing the particle size of the polymer. Undercoating was another suitable measure to decrease the amount of coating material required. The choice of plasticizer was of special importance in the aqueous dispersions, and type and quantity must be appropriate for the polymer applied. Non-polymeric plasticizers such as triethyl citrate (TEC) evaporated along with water during the spraying or drying process and high temperatures promoted such losses. The moisture-sensitive pancreatic enzymes were damaged both by humidity and heat during aqueous coating. The extent of damage was dependent on the coating equipment used. Upon storage, coatings obtained from aqueous dispersions showed changes in enteric performance or release characteristics as a consequence of three chemical/physical mechanisms: hydrolysis of ester linkages in the polymer or plasticizer, evaporation of the plasticizer, delayed film formation. The active ingredient pancreatin induced hydrolysis of the ester based film-former hydroxypropyl methylcellulose acetate succinate (HPMCAS). However, even without the influence of enzymes, the phthalic ester groups of aqueous hydroxypropyl methylcellulose phthalate (HP) were partly cleaved after 11 months storage. In HPMCAS-coated pancreatin pellets, the plasticizer glyceryl triacetate was almost completely hydrolyzed by the enzymes, whilst triethyl citrate was lost by evaporation through permeable packaging material at elevated temperatures. Open storage at elevated temperatures and humidities caused changes in the surface structure of HPMCAS coatings, consisting of a smoothing of the originally somewhat porous film and sticking. When applied to vitamin B 2 tablets, Eudragit® L 100-55, Opadry® enteric (PVAP) and Aqoat® (HPMCAS) proved to be quite stable aqueous enteric coatings, whereas cellulose acetate phthalate CAP or cellulose acetate trimellitate CAT coatings as ammonia-neutralized aqueous solution or as water-based pseudolatex Aquateric® were unstable when stored under stress conditions.

Characterization and bioavailability of danazol-hydroxypropyl β-cyclodextrin coprecipitates

Danazol, a steroid with very low aqueous solubility and poor bioavailability, and its coprecipitates were characterized for solubility, dissolution rate and bioavailability. Solubility diagrams of danazol in aqueous hydrox-ypropyl β-cyclodextrin (HPCD) solutions and isopropanol/water solutions were constructed with concentration of HPCD solutions ranging between 0.65 and 65.0 mM. Coprecipitates of danazol and HPCD at ratios ranging from 1:1 to 1:10 were prepared by solvent evaporation method using ethanol and by freeze drying method. Solubility diagrams indicated the existence of a complex between danazol and HPCD, and showed a remarkable increase in danazol solubility. Stability constants of the complex and thermodynamic parameters of complexation were calculated in both aqueous and aqueous / organic solvents; the presence of isopropanol appeared to have negative effect on the stability of the complex. Dissolution profiles of the coprecipitates demonstrated higher dissolution rates than pure danazol.Characterization of coprecipitates by DSC and X-ray diffraction techniques showed that danazol existed almost exclusively in crystalline form in coprecipitates at low danazol to HPCD ratios; while at high ratios, danazol appeared to exist in a non-crystalline form. No distinct differences in the product characteristics could be attributed to the method of preparation. Oral bioavailability of the coprecipitate (danazol: HPCD, 1:10) and a marketed danazol were tested in Wistar rats in a two-way, randomized cross-over study. The area under the curve (AUC) of plasma concentration versus time was significantly higher ( P < 0.05) for the complex than the commercial formulation, with mean AUC value more than two-fold higher for the complex. The bioavailability of the coprecipitate relative to the commercial formulation was calculated to be 237%. The peak plasma concentration ( C max) of the coprecipitate was higher and the time to reach the peak ( T max) was lower for the complex. The greater rate and extent of absorption of danazol from the complex makes it a formulation with the potential to decrease the oral dose of danazol. Absolute bioavailability of the coprecipitate and commercial formulation was 14.2% and 6.2%, respectively.

Transition of viscous fingering patterns in polymer solutions

Viscous fingering patterns of aqueous hydroxypropyl methyl cellulose (HPMC) solutions pushed by air in the Hele–Shaw cell were observed as a function of isopropyl alcohol content under a constant pressure of 15 cm H2O. A morphological transition from side branching patterns to tip splitting ones with increasing isopropyl alcohol content, accompanied with a decrease in surface tension and an increase in viscosity is found. The observed morphology transition was correlated with the dimension of the fingering pattern, as well as the average tip velocity in the fingering.

The mechanical and moisture permeability properties of aqueous-based hydroxypropyl methylcellulose coating systems plasticized with polyethylene glycol

The effects of polyethylene glycols (PEG 400, 1500 and 4000) used as plasticizer on the moisture permeability and mechanical properties of aqueous hydroxypropyl methylcellulose (HPMC) films were evaluated with free films. The free films were prepared by using a pneumatic spraying technique similar to that used in fluidized-bed coaters. There was a clear relationship between some physical film properties and the molecular weights and concentrations of the PEGs used as plasticizer. Over the range of concentrations tested, the moisture permeability of the films decreased slightly as compared to unplasticized control films with increasing molecular weight of the plasticizer. The mechanical strength of the films was shown to be more dependent on the concentration than on the molecular weight of the PEGs, while the ductility of the films was mainly dependent on the molecular weight of the PEG. The addition of PEG at a concentration of 10% resulted in relatively hard and strong films with a moderate elongation (ductility), especially when lower molecular weight plasticizers (PEG 400 or 1500) were used. As regards permeability to moisture and mechanical properties, the addition of PEG at a concentration in the range of 10–20% of the polymer weight seems to be beneficial for aqueous-based HPMC film coats.

Effects of polymer adsorption and desorption on rheological properties of silica suspensions

Shear stresses and dynamic moduli of silica suspensions in aqueous hydroxypropyl methyl cellulose (HPMC) solutions were measured by using a cone-plate geometry as functions of the concentrations of silica, HPMC, isopropyl alcohol, acetic acid and pyridine. Isopropyl alcohol and pyridine behaved as displacers and they cause desorption of HPMC from the silica surfaces. The amounts of HPMC adsorbed on the silica surfaces decrease with an increase in the displacer concentration. In plots of steady state shear stress against shear rate, there was a shear rate of about 0.1 s −1 due to aggregation of the silica particles and this did not disappear on addition of isopropyl alcohol or acetic acid. However, the silica suspensions with pyridine must show some stress responses, although these may be outside the measurement range for the instrument. Pyridine increases the pH in the dispersion, leading to stable and unaggregated silica particles. By adding isopropyl alcohol to the silica suspensions, the storage modulus decreases with the amount of HPMC desorbed from the silica surfaces. The larger amounts of HPMC desorbed resulted in no second plateau in the dynamic moduli, showing the weaker aggregated structures in the silica suspensions. In contrast, pyridine had no detectable effect on the dynamic moduli of the silica suspensions.

Plasticization of aqueous poly(vinyl alcohol) and hydroxypropyl methylcellulose with polyethylene glycols and glycerol

The plasticization of aqueous hydroxypropyl methylcellulose (HPMC) and poly(vinyl alcohol) (PVA) with poly(ethylene glycols) (PEGs) with various molecular weights and with glycerol has been investigated. The plasticizing efficiency in the case of HPMC was: PEG200 > PEG400 > GLYCEROL > PEG6000 and for PVA: GLYCEROL > PEG200 > PEG400 > PEG6000. The plasticizer efficiency rating was explained with the partial solubility parameters of the polymers and the plasticizers in terms of the propensity of each polymer-plasticizer pair to set up polar and hydrogen-bonding interactions. Phase separation of the plasticizers occurred above a critical concentration which, in the case of PEGs, was inversely proportional to molecular weight. Phase separation of the plasticizer was shown to be responsible for deterioration in the plasticizing efficiency.

Liquid crystal‐forming aqueous hydroxypropyl cellulose solutions: Effects of surfactants on the turbidity and shear viscosity

AbstractThe effects of type and concentration of surfactant on the turbidity and viscometric behavior for dilute and concentrated aqueous hydroxypropyl cellulose (HPC) solutions were examined. Two anionic surfactants, sodium dodecyl benzene sulfonate (SDBS) and sodium dodecyl sulfate (SDS), caused the cloud point of the dilute system to increase, but a nonionic and two cationic surfactants did not do so markedly. The transmittance for the dilute system increased with surfactant. The transmittance and viscometric behavior for the concentrated system were strongly dependent on the phase of the system: In the single‐phase (isotropic and anisotropic), the transmittance and viscosity increased with SDBS, but, in the biphasic region, the behaviors were not as simple. An attempt was made to explain the transmittance and viscometric behavior in the single‐phase on the basis of the change in apparent molecular weight and in order of HPC molecules. The phase transformation appeared to become less sensitive to temperature with SDBS. © 1993 John Wiley &amp; Sons, Inc.

Transient and steady-state rheology of silica suspensions in hydroxypropyl(methyl)cellulose solutions

Coaxial cylinder rheological measurements have been performed on Aerosil silica suspensions in aqueous hydroxypropyl(methyl)cellulose (HPMC) solutions as functions of both HPMC and silica concentrations for two HPMC samples. Adsorption isotherms of HPMC at the silica particles were measured for various silica contents. In transient experiments rheopexy was found for 5% silica suspensions and stress overshooting behaviour was observed for 7.5% silica suspensions. In the steady-state experiments, a bump was observed at near the shear rates of 0.1 s–1 in the plot of the steady-state shear stress for 7.5% silica suspensions against the shear rate. Appearance of the bump was attributed to the aggregation characteristics of the silica and it was not influenced by desorption of HPMC from the silica surfaces. Dynamic experiments showed that when the silica content was low, showing a more open network of the aggregated silica, the viscoelastic property of the silica suspension changed from a solid-like to a liquid-like character with increasing frequency. When the silica content was high, indicating a less open network of the structure, the silica suspensions showed a solid-like viscoelastic character. Desorption of HPMC led to a decrease in the viscoelastic moduli.

Phase separation and polymer interactions in aqueous poly(vinyl alcohol)/hydroxypropyl methylcellulose blends

This paper discusses the compatibility of aqueous hydroxypropyl methylcellulose (HPMC)/poly(vinyl alcohol) (PVA) blended systems. Dynamic mechanical analysis and differential scanning calorimetry have provided clear evidence of two phases. Each phase precluded almost completely the other component. The HPMC-rich phase was amorphous with a constant T g while the PVA-rich phase showed a limited level of crystallinity and a constant T g for the amorphous part. Fourier-transform infra-red studies indicated hydrogen-bonding interactions involving the carbonyl and hydroxyl groups of like molecules but no detectable interactions between HPMC and PVA. A new hydrogen-bonding environment of the hydroxyls was observed in the blended system but was not capable of inducing any compatibility. The gross incompatibility was successfully predicted by the total solubility parameters of the two polymers and attributed to significant differences in the polar and hydrogen-bonding contributions. Surface energy analysis corroborated the inability of the two chains to participate in acid-base interactions between unlike molecules due to significant discrepancies in their Lewis acid-base characteristics. Finally, determination of the free energy of polymer-polymer interaction in water allowed approximate calculation of the Flory-Huggins parameters of aqueous PVA and HPMC systems.

Cholesteric pitch of aqueous hydroxypropylcellulose in the presence of synthetic polyelectrolytes

Cholesteric pitches (D) of mesophases of aqueous hydroxypropyl cellulose (HPC) have been measured by the reflection spectrum method in the presence of simple- and poly-electrolytes. The simple electrolytes used were sodium chloride and sodium sulphate, the polyelectrolytes were sodium poly(ethene sulphonate)(NaPES), sodium poly(styrene sulphonate)(NaPSS), polybrene (PB), poly(4-vinyl-N-benzylpyridinium chloride)(BzPVP), and a copolymer of 4-vinyl-N-hexadecylpyridinium bromide and 4-vinyl-N-benzylpyridinium chloride (C16BzPVP). NaCl and Na2SO4 decrease D values, explained by the desolvation effect of the salts upon HPC molecules. Cationic macro-ions also decrease D values, and the strength of the effect is in the order PB > BzPVP > C16BzPVP. This is due to the shrinkage of the HPC helicoid by the association of HPC with the macrocations. On the other hand, anionic polyelectrolytes increase D values in the order NaPSS > NaPES, which is ascribed to the intercalation of the macro-anions into the intra-chain space of the helicoidal HPC by the hydrophobic interaction.

TRANSMISSION ELECTRON MICROSCOPY OF AQUEOUS POLYMER GEL NETWORK MORPHOLOGY

Freeze-fracture TEM images of polymer network structure in aqueous hydroxypropyl guar (HPG) gels permit direct correlations between observed gel morphology and macroscopic chemical and mechanical properties. HPG in aqueous solution associates via hydrogen bonding, even without titanate crosslinker, to form an extended network, the structure of which depends on the electrolyte concentration. The titanate crosslinker acts only to weld together polymer molecules already associated by hydrogen bonding. Mechanical shear degrades the gel by breaking up the network inhomogeneously to form “fractured gel particles,” small domains of well-crosslinked gel separated by fluid domains.

Effect of Storage on the Properties of Acetylsalicylic acid Tablets Coated with Aqueous Hydroxypropyl Methyl-Cellulose Dispersion

AbstractThe objective of this study was to investigate whether the properties of acetylsalicylic acid tablets coated with aqueous hydroxypropyl methylcellulose dispersion using glycerol or polyethylene glycol 6000 as plasticizer change during storage at 25° or 40°C. Titanium dioxide was used as pigment. The tablets were coated in a fluid bed apparatus. The disintegration time and the release of acetylsalicylic acid during two hours were determined for both uncoated and coated tablets immediately after their preparation and after different storage periods.When the tablets were stored at room temperature (25°C) the coat protected the core efficiently against changes in the measured parameters as compared with uncoated tablets. However, at higher temperature (40°C) some unfavorable phenomena occurred in the coat and after storage of 48 months, the disintegration time was longer and the dissolution of acetylsalicylic acid slower than from uncoated tablets. Polyethylene glycol was found to be a better protecti...

The surface tension of aqueous hydroxypropyl cellulose solutions

The surface tension of aqueous solutions of hydroxypropyl cellulose has been measured using the pendant drop method. Hydroxypropyl cellulose samples with molecular weights greater than 100,000 gave a steady-state surface tension of 42.4 ± 1.0 mN/m for all concentrations ranging from 2 ppm to 32% by weight. Samples of lower MW hydroxypropyl cellulose also gave this surface tension at all but the lowest (<10 ppm) concentrations. The changes in surface tension with time were compared with the rates of diffusion of the solutes, which were measured interferometrically. At low solute concentrations, surface tension-time curves followed a sigmoidal pattern, with a well-defined induction period. An equation, formally similar to the Avrami equation for the nucleation and growth of crystalline phases, was found to correlate the changes in surface tension with time, solute concentration, and solute diffusion rates.