Absence Of Hydroxypropyl Methylcellulose Research Articles

Effects of redispersible polymer powders on the structural build-up of 3D printing cement paste with and without hydroxypropyl methylcellulose

This paper studies the effects of polyvinyl acetate-ethylene (VAE) based redispersible polymer powder (RPP) and polyvinyl acetate-vinyl versatate-ethylene (VVE) based RPP on the structural build-up of 3D printing cement paste within several hours of hydration. At the same time, two cases of the presence or absence of hydroxypropyl methylcellulose (HPMC) were considered. The build-up performance of cement paste was assessed by the hysteresis area, dynamic yield stress ratio, static yield stress, shear modulus and ultrasonic plus velocity from the dynamic shear test, static shear test and ultrasonic wave transmission test. In addition, the limit layer thickness and printing velocity were calculated by dynamic and static yield stresses to quantitatively characterize shape stability and printing efficiency of cement paste. Results indicate that both VAE with higher ethylene content (VAE1) and VVE decrease the structural build-up rate of cement paste, independent of shear test modes. However, VAE with lower ethylene content (VAE2) increases the structural build-up rate of cement paste under dynamic shear test whereas decreases the growth rate of static yield stress. The dynamic yield stress ratio of cement paste containing 2% VAE2 is 0.57, which is 83.9% higher than that of pure cement paste. In addition, HPMC alters the effects of VAE2 on the structural build-up of cement paste. VAE1 and VVE decrease the shape stability of cement pastes with and without HPMC, while VAE2 is beneficial to the shape stability of cement paste. Limit layer thicknesses of cement pastes with 4% VAE2 are 7.3 mm and 14 mm in the absence and presence of HPMC, which are about 3.0 and 5.8 times that of pure cement paste. In the absence of HPMC, VVE decreases the limit printing velocity of cement paste in the first tens of minutes. VAE1 and VAE2 can improve the printing efficiency due to the increase of limit printing velocity in the first tens of minutes. In the presence of HPMC, only VAE2 significantly improves the limit printing velocity of cement paste.

Effects of Coformer and Polymer on Particle Surface Solution-Mediated Phase Transformation of Cocrystals in Aqueous Media.

The purpose of the present study was to investigate the effect of the coformer difference on particle surface solution-mediated phase transformation (PS-SMPT) during cocrystal particle dissolution in aqueous media in the absence and presence of polymers. SMPT can occur either in the bulk phase or at the particle surface because drug molecules can be supersaturated at the dissolving cocrystal surface, as well as in the bulk phase. Previously, bulk phase SMPT has been primarily investigated in formulation development. However, little is known about the effects of coformers and polymers on PS-SMPT of cocrystals. In this study, six carbamazepine (CBZ) cocrystals were used as model cocrystals (malonic acid (MAL), succinic acid (SUC), glutaric acid (GLA), adipic acid (ADP), saccharin (SAC), and nicotinamide (NCT); nonsink dissolution tests were performed with or without a precipitation inhibitor (hydroxypropyl methylcellulose (HPMC)) at pH 6.5. The residual particles were analyzed by powder X-ray diffraction, differential scanning calorimetry, polarized light microscopy (PLM), and scanning electron microscopy. Real-time PLM was used to directly observe rapid PS-SMPT. In the absence of HPMC, supersaturation was not observed in the bulk phase for all cocrystals. All cocrystals rapidly transformed to CBZ dihydrate aggregates via PS-SMPT (mostly within 1 min). In contrast, in the presence of 0.1% HPMC, supersaturation was observed for CBZ-SUC, CBZ-ADP, CBZ-SAC, and CBZ-NCT but not for CBZ-MAL and CBZ-GLA. The cocrystals with lower solubility coformers tended to induce higher supersaturation in the bulk phase. The PS-SMPT of CBZ-SUC, CBZ-ADP, and CBZ-SAC was slowed down by HPMC. By suppressing PS-SMPT, the cocrystals exhibited its supersaturation potential, depending on the properties of each coformer. To take advantage of the supersaturation potential of cocrystals to improve oral drug absorption, it is important to suppress particle surface SMPT in addition to bulk phase SMPT.

In-situ forming composite implants for periodontitis treatment: How the formulation determines system performance

Periodontitis is the primary cause of tooth loss in adults and a very wide-spread disease. Recently, composite implants, based on a drug release rate controlling polymer and an adhesive polymer, have been proposed for an efficient local drug treatment. However, the processes involved in implant formation and the control of drug release in these composite systems are complex and the relationships between the systems’ composition and the implants’ performance are yet unclear. In this study, advanced characterization techniques (e.g., electron paramagnetic resonance, EPR) were applied to better understand the in-situ forming implants based on: (i) different types of poly(lactic-co-glycolic acid) (PLGA) as drug release rate controlling polymers; (ii) hydroxypropyl methylcellulose (HPMC) as adhesive polymer; and (iii) doxycycline or metronidazole as drugs. Interestingly, HPMC addition to shorter chain PLGA slightly slows down drug release, whereas in the case of longer chain PLGA the release rate substantially increases. This opposite impact on drug release was rather surprising, since the only difference in the formulations was the polymer molecular weight of the PLGA. Based on the physico-chemical analyses, the underlying mechanisms could be explained as follows: since longer chain PLGA is more hydrophobic than shorter chain PLGA, the addition of HPMC leads to a much more pronounced facilitation of water penetration into the system (as evidenced by EPR). This and the higher polymer lipophilicity result in more rapid PLGA precipitation and a more porous inner implant structure. Consequently, drug release is accelerated. In contrast, water penetration into formulations based on shorter chain PLGA is rather similar in the presence and absence of HPMC and the resulting implants are much less porous than those based on longer chain PLGA.

Technical Note: Non-Sink Dissolution Media for Identification of Functional Formulation Excipients—The Case of a Precipitation Inhibitor

INTRODUCTION Due to the abundance of dissolution methodology and media available to pharmaceutical development and quality scientists, it is advisable that method selection criteria be dictated by the purpose of the measurement. This is particularly important when dissolution is used as a tool to guide formulation design. These cases often require the use of conditions that are relevant to the in vivo situation, but most critically, they are chosen to tease out an excipient’s ability to perform its intended function. This note aims to illustrate how purposeful media selection can help probe the functionality of an excipient to be used in a solid oral dosage form of a low solubility compound. In this example, the active pharmaceutical ingredient (API) is a crystalline potassium salt of a weak acid with a pKa = 6.8, and the excipient in question is hydroxypropyl methylcellulose (HPMC). The API has relatively high solubility, 71 mg/ mL in water or at a pH > pKa, which drops to 0.01 mg/ mL (the equilibrium solubility of the protonated free form measured more than 24 h after the crystalline salt was introduced in aqueous medium) at pH < 6.8, the pH expected in the gastrointestinal (GI) tract (1). The HPMC excipient was chosen for its potential ability to act as an antinucleating agent (2), inhibit precipitation of the drug at a pH < pKa, and induce super saturation, thus enhancing in vivo solubility and absorption. To assess the utility of the excipient for an oral dosage form, in vitro dissolution of the neat API is carried out under non-sink conditions, at a pH < pKa and a dose-relevant concentration, in the presence and absence of HPMC. Next, dissolution of the formulated API is carried out under non-sink conditions, over a pH range that is GI relevant, at dose-relevant concentrations. Subsequently, preclinical models are used to assess further the in vivo utility of the HPMC excipient before defining a formulation for human trials. A range of drug and excipient concentrations may be explored in vitro depending on predicted clinical doses and dosage form considerations, respectively. Two examples of in vitro measurements of neat and formulated API are presented below.

Modulated dissolution rate from the inclusion complex of antichagasic benznidazole and cyclodextrin using hydrophilic polymer

Benznidazole (BNZ) is the primary chemotherapeutic agent for treating Chagas’ disease; however, its poor water solubility and irregular oral absorption lead to the treatment failure in the chronic phase. The aim of this work was to investigate the utility of the polymer hydroxypropyl methylcellulose (HPMC) in controlling the release of BNZ from solid inclusion complexes with cyclodextrin to overcome the problem of its bioavailability. Preliminary studies of solubility were conducted in solution using selected β-cyclodextrin derivatives according to an experimental mixture design. The best cyclodextrin composition was used to produce solid-state systems by kneading in the presence or absence of HPMC. The formulations were characterized by different physico-chemical techniques, including the dissolution rate. Hydroxypropyl-β-cyclodextrin (HPβCD) produced the greatest improvement in drug solubility and was selected for the development of solid systems. Assays confirmed the production of true inclusion complexes between BNZ and HPβCD. The dissolution rate of the BNZ-HPβCD system was markedly increased, while the presence of HPMC retarded drug release. An optimal formulation obtained by the combination of kneading systems developed in appropriate ratios could be a promising drug delivery system with a prolonged therapeutic effect coupled with more balanced bioavailability. The produced systems present interesting perspectives for Chagas’ therapy.

Effect of pH and water-soluble polymers on the aqueous solubility of nimesulide in the absence and presence of &lt;I&gt;β&lt;/I&gt;-cyclodextrin derivatives

The aqueous solubility of nimesulide in the absence and presence of beta-cyclodextrin (beta-CD) and its alkyl derivatives hydroxypropyl-beta-CD and methyl-beta-CD was studied. We also investigated the effect of water-soluble polymers, hydroxypropylmethyl-cellulose, sodium-carboxymethyl-cellulose, polyvinylpyrrolidone and polyethyleneglycol on the solubilization efficacy and complexation ability of cyclodextrins with nimesulide. The solubility of nimesulide in the absence and presence of cyclodextrins and polymers was studied using a phase solubility technique combined with a spectrophotometric method. The study was carried out at 25 degrees C and pH values of 6.0 and 7.0. Conditions in terms of polymer concentration and polymer heating with and without sonication were optimized. Values of the solubility enhancement factor of nimesulide in the presence of each cyclodextrin and in the absence and presence of each polymer were determined and the formation constants, K, of the inclusion complexes formed calculated. beta-CDs increased the aqueous solubility of nimesulide in the following order: methyl-beta-CD > beta-CD > hydroxypropyl-beta-CD. Addition of hydroxypropylmethyl-cellulose at a concentration of 0.1% (w/v) had the greatest influence on complexation of all three beta-CDs with nimesulide, while preheating of the polymer at 70 degrees C under sonication resulted in an additional two-fold increase in the aqueous solubility of the drug. Sodium-carboxymethyl-cellulose, polyvinylpyrrolidone and polyethyleneglycol had minor effects on the aqueous solubility of nimesulide. Thus beta-CD, hydroxypropyl-beta-CD and methyl-beta-CD are proposed as good solubilizing agents for nimesulide in the presence and absence of hydroxypropylmethyl-cellulose in order to enhance its oral bioavailability.

Electrosteric stabilization of concentrated cement suspensions imparted by a strong anionic polyelectrolyte and a non-ionic polymer

Strong polyelectrolytes, known as superplasticizers, improve the initial fluidity of concentrated cement suspensions through electrostatic stabilization. These polyelectrolytes do not maintain the initial fluidity, however, primarily due to an increase in the ionic strength of the cementitious suspension. Consequently, non-ionic polymers are often used in conjunction with polyelectrolytes to provide steric stabilization and hence to sustain the desired fluidity over a longer time, and this has lead to the development of copolymers with both electrostatic and steric (electrosteric) functionalities. To design such polymers, it is necessary to optimize the balance between electrostatic and steric stabilization to maximize suspension fluidity. We have quantified the effects of a strong anionic polyelectrolyte, melamine formaldehyde sulfonate (MFS), and a non-ionic polymer, hydroxypropylmethylcellulose (HPMC), on the zeta potential of cement particles and the steady shear and low-amplitude rheological properties of concentrated cement suspensions. While the adsorption of MFS onto the cement particle surfaces leads to a sign inversion in the zeta potential, the adsorption of the non-ionic HPMC has no significant effect on the potential. The addition of HPMC to the suspensions substantially reduces the steady shear viscosity and the storage modulus at constant MFS concentration; in addition, there exists an intermediate HPMC concentration that minimizes fluidity. The resulting suspension fluidity is also maintained over a longer time than in the absence of HPMC. This improvement in the stability and fluidity of cement suspensions is attributed to “complementary electrosteric dispersion/stabilization”, and provides insight to the design of polymers with electrosteric functionality.

Different approaches for increasing the shelf life of partially baked bread: Low temperatures and hydrocolloid addition

Partially baked bread is a product with short shelf life that requires sub-zero temperatures for extending it. The storage of par-baked bread at low temperatures and the addition of bread improvers with antistaling effects, such as hydroxypropylmethylcellulose (HPMC), are very attractive alternatives for extending the shelf life of these products. In this study, staling during storage of partially baked bread (in the presence and absence of HPMC) at low temperatures (2 °C) is studied in terms of hardness increase and amylopectin retrogradation. Simultaneously, the staling of the derived full baked breads when stored at 25 °C is assessed. During the storage of par-baked bread at low temperatures, progressive crumb hardening and rapid crystallization of the amylopectin chains were produced. However, heat applied during full baking reversed those processes, and the extent of that improvement was dependent on the time of par-baked bread storage. Concerning the staling of the derived full baked bread, the time of par-baked bread storage did not significantly ( P < 0.05) affect the staling process of the resulting full baked breads. The addition of HPMC decreased the crumb hardness in both par-baked and full baked breads, and also promoted a reduction of the amylopectin retrogradation. Overall results indicate that HPMC addition significantly retards the staling of par-baked bread during its storage at low temperatures and, moreover, the same effect is observed in the full baked bread.

Different approaches for improving the quality and extending the shelf life of the partially baked bread: low temperatures and HPMC addition

The use of refrigeration or positive temperature storage as an alternative to frozen storage for extending the shelf life of partially baked bread is described. In addition, the effect of hydroxypropylmethylcellulose (HPMC) on the baking performance of those products is detailed. With this purpose, the quality and shelf life of the bread from partially baked bread stored at frozen temperatures (−25 °C) for 42 days was compared with those of that from positive temperature stored partially baked bread (2 °C) stored for 10 days. In both cases, batches in the presence and absence of HPMC were performed. The characteristics evaluated were the microstructure by cryo-scanning electron microscopy (cryo-SEM), the sensory quality, the technological properties (specific volume, moisture content, width/height ratio, crumb hardness), the crumb grain and the staling rate. The microstructure of the bread crumb from the positive temperature stored sample was almost intact compared with that of the bread from its frozen counterpart. The positive temperature storage led to bread with better specific volume, low crumb hardness and slower hardening rate during staling than the bread stored at frozen temperatures. Regarding the sensory quality, loaves from positive temperature stored par-baked bread did not differ in appearance and aroma, but had lower scores in taste and texture than the samples from frozen par-baked bread. The presence of HPMC improved the technological parameters and diminished the staling rate without affecting the sensory attributes. The beneficial effect of the HPMC was more evident on the samples from frozen par-baked bread, showing a microstructure without any damage due to ice crystals growth and similar to that observed in the samples from positive temperature stored par-baked bread.

Release of Propranolol Hydrochloride from Matrix Tablets Containing Sodium Carboxymethylcellulose and Hydroxypropylmethylcellulose

Hydroxypropylmethylcellulose (HPMC) and three viscosity grades of sodium carboxymethylcellulose (NaCMC), namely NaCMC (Blanose 7H 4XF®), NaCMC (Courlose P 800®), and NaCMC (Courlose P 350®), were investigated for their ability to provide a sustained release of propranolol hydrochloride from matrices. The rank order of release rate, in the absence of HPMC, was NaCMC (Blanose) < NaCMC P 800 < NaCMC P 350 for matrices containing 95–285 mg NaCMC, and was dependent on their viscosity grades. The effects of changing the ratio of HPMC to NaCMC (Blanose) and the drug/total polymer ratio were examined. The release rates decreased as the proportion of NaCMC in the matrices increased. Zero-order release of propranolol hydrochloride was obtained from matrices containing 285 mg 3:1 NaCMC (Blanose)/HPMC. Differential scanning calorimetry was used to quantify the moisture uptake by the polymers at 37°C. Wafers containing NaCMC (Blanose) or 1:1 HPMC/NaCMC (Blanose) absorbed water similarly. A study of the erosion rates of matrices containing polymer only indicated that NaCMC (Blanose) eroded more quickly than HPMC. When propranolol hydrochloride was included in matrices containing NaCMC (Blanose), the erosion was reduced as a result of the insolubility of a complex formed between NaCMC and propranolol hydrochloride. The interaction between propranolol hydrochloride and NaCMC (Blanose) was confirmed by both dialysis and by monitoring the release of sodium ions from the matrices.

The effect of HPMC—a cholesterol‐lowering agent—on oral drug absorption in dogs

The objective of this study was to evaluate the effects which hydroxypropylmethylcellulose (HPMC) may exert on oral drug absorption, in cases where this soluble fiber is administered to regulate blood lipid levels. Studies were conducted in vitro and in healthy female mongrel dogs using two different grades of HPMC, i.e. K8515 HPMC and ultra high molecular weight (UHMW) HPMC. The maximum plasma concentration, Cmax, of paracetamol and both the Cmax and the area under the concentration–time curve, AUC, of cimetidine were significantly decreased by the coadministration of 10 g of K8515 HPMC or 7.5 g of UHMW HPMC dissolved in 500 mL normal saline under fasting conditions. No statistically significant effects were observed on hydrochlorothiazide or mefenamic acid absorption. Based on in vitro data and previous studies it appears that reductions in gastric emptying and dissolution rate of paracetamol account for the effect observed in vivo. For cimetidine, a drug which can be absorbed from both the small and the large intestine, the indigestibility of HPMC in the colon in addition to the great reduction of dissolution rate led to reductions of both the Cmax and AUC values. The long Tmax values, even in the absence of HPMCs and the more modest reduction of the dissolution rate of hydrochlorothiazide by the HPMCs are thought to have precluded the observation of any significant alterations in the in vivo absorption profile. Owing to its erratic absorption, no statistically based conclusion could be drawn about the effects of coadministered HPMC on the oral absorption of the poorly soluble mefenamic acid. It is concluded that the effects of HPMCs on drug absorption in dogs are most pronounced for compounds with absorption profiles that are dependent on gastric emptying, i.e. compounds that are highly water soluble and that exhibit short Tmax values. Compounds with long absorption profiles appear to be less susceptible to changes in absorption behavior due to coadministration of HPMCs. Copyright © 1998 John Wiley & Sons, Ltd.

The effect of HPMC—a cholesterol-lowering agent—on oral drug absorption in dogs

The objective of this study was to evaluate the effects which hydroxypropylmethylcellulose (HPMC) may exert on oral drug absorption, in cases where this soluble fiber is administered to regulate blood lipid levels. Studies were conducted in vitro and in healthy female mongrel dogs using two different grades of HPMC, i.e. K8515 HPMC and ultra high molecular weight (UHMW) HPMC. The maximum plasma concentration, Cmax, of paracetamol and both the Cmax and the area under the concentration-time curve, AUC, of cimetidine were significantly decreased by the coadministration of 10 g of K8515 HPMC or 7.5 g of UHMW HPMC dissolved in 500 mL normal saline under fasting conditions. No statistically significant effects were observed on hydrochlorothiazide or mefenamic acid absorption. Based on in vitro data and previous studies it appears that reductions in gastric emptying and dissolution rate of paracetamol account for the effect observed in vivo. For cimetidine, a drug which can be absorbed from both the small and the large intestine, the indigestibility of HPMC in the colon in addition to the great reduction of dissolution rate led to reductions of both the Cmax and AUC values. The long Tmax values, even in the absence of HPMCs and the more modest reduction of the dissolution rate of hydrochlorothiazide by the HPMCs are thought to have precluded the observation of any significant alterations in the in vivo absorption profile. Owing to its erratic absorption, no statistically based conclusion could be drawn about the effects of coadministered HPMC on the oral absorption of the poorly soluble mefenamic acid. It is concluded that the effects of HPMCs on drug absorption in dogs are most pronounced for compounds with absorption profiles that are dependent on gastric emptying, i.e. compounds that are highly water soluble and that exhibit short Tmax values. Compounds with long absorption profiles appear to be less susceptible to changes in absorption behavior due to coadministration of HPMCs.

Ultraviolet detector response of glycine and alanine homopeptides: Some specific features in capillary electrophoresis

UV absorbance of a single peptide bond contribution at 200 nm to the overall optical density of the solute was evaluated with two sets of model peptides composed of either 1–14 glycine or alanine residues. It was documented that in capillary electrophoresis using 57 cm (50 cm to the detector) ×75 μm i.d. capillary and 25 mmol l phosphate buffer pH 2.5 containing or devoid of 0.35% hydroxypropyl-methylcellulose (HPMC), the detector's response per peptide bond drops down in peptides containing five glycine or alanine residues. This limiting absorbance value was shown to increase again with the increasing length of the peptide chain reaching either a constant value (glycine and alanine peptides) run in the absence of HPMC at elevated (50°C) temperature or exhibiting a second stepped drop with alanine peptides run at 25°C or in the presence of the polymeric sugar in the background electrolyte. The reasons of this hypochromic effect are discussed.

Bead cellulose products with film formers and solubilizers for controlled drug release

Flowable bead cellulose (BC) coprecipitates were prepared for controlled release, consisting of spherical BC as carrier, the film former hydroxypropyl methylcellulose (HPMC), the hydrophilic solubilizers polyethylene glycol 6000 (PEG 6000) or Poloxamer, the plasticizers dimethyl phthalate and dioctyl phthalate and the model drugs prednisolone and griseofulvin. Coprecipitates of BC/HPMC/drug or BC/HPMC/plasticizer/drug without solubilizer showed fast and complete release of prednisolone due to the dispersed crystalline state and sufficient solubility of the drug and retarded release of griseofulvin due to poor solubility. The drugs crystallized during coprecipitation and were partially incorporated as well as HPMC and plasticizer into the pores of the beads and precipitated on the bead surface. IR-dried coprecipitates of BC, high solubilizer content and low HPMC content (or absence of HPMC) showed high release rates due to the amorphous or solid dispersed state of the drugs in the coprecipitates, therefore fast dissolution due to the solubilizing effect of PEG 6000 or Poloxamer. On the other hand, with increasing HPMC content and decreasing solubilizer content the release rates were diminished due to increasing crystallinity of the drugs and therefore slow dissolution, reduced solubilization, swelling of HPMC and hindered drug diffusion. The IR-dried coprecipitates with solubilizers were flowable and consisted of spherical particles. Freeze-dried coprecipitates of similar composition consisted of beads and separate HPMC and solubilizer particles. The advantages of the BC coprecipitates are the variation of the release rates in a wide range by changing the ratio of solubilizer, HPMC and drug and their favourable physical and flow properties.