HPMC Solution Research Articles

3D printing Si3N4-bonded SiC refractories fabricated using colloidal films-containing slurries based on non-spherical SiC and Si powders

Stable slurries for Si3N4-bonded SiC refractories for direct ink writing (DIW) were successfully prepared from a mixture of non-spherical silicon carbide (SiC) and silicon (Si) powders with an average particle size of D50 = 41.98 μm. The rheological properties and printability of slurries prepared using polyvinyl alcohol (PVA; 4–16 wt %) or hydroxypropyl methylcellulose (HPMC, 0.5–2 wt.%) were investigated with the effect of sintering temperature on the mechanical performance, phase, and microstructure of Si3N4-bonded SiC refractory products. The results indicated that slurries prepared with the HPMC solution showed better printability than those prepared with the PVA solution because colloidal films formed by HPMC in slurries play a role in encasing particles, preventing solid−liquid separation and contributing to plasticity and lubrication, which guarantees the smooth extrusion and homogeneity of slurries. The successful printing of SiC–Si slurries is not only related to proper viscosity, yield value, and shear thinning characteristics but it is also crucial for maintaining the homogeneity of slurries under extrusion pressure. Optimal SiC–Si slurries containing 52 vol % SiC–Si and 1.5 wt% HPMC exhibited proper viscosity, shear thinning, and homogeneity characteristics during printing. The obtained specimens achieved the best printing performance with height and section retention rates of 98.7% and 97.6%, respectively. When sintered at 1450 °C, Si3N4 fibres grow further and reach a diameter of 342.5 nm, the nitriding rate is 92.43%, the fibres tend to form a full network structure, and the mechanical properties of Si3N4-bonded SiC products are the best.

STUDY AND SELECTION OF A MODEL SOLUTION CONTAINING ANTIBIOTICS TO DEVELOP AN EAR DROP TO TREAT OTITIS MEDIA

Introduction. Otitis media is an infection of the middle ear, it happens in the space behind the eardrum which contains the tiny vibrating bones of the ear. it divided into acute otitis media (AOM), suppurative otitis media (SOM) and otitis media with effusion (OME). Otitis is the most common specific disease in children, children aged 0–12 registered in 62 practices (1 March 2019–29 February 2020) and (1 March 2020–28 February 2021) were includ-ed, and secondly, the problem of treating acute otitis media in of adults remains one of the most urgent problems of modern otolaryngology, treat-ment may begin with clear up pain and sometimes, antibiotics are used to clear the infection. The aim of the study – development of a therapeutic solution containing an antibiotic from fluoroquinolones group for the treatment of acute otitis media. Material and methods. Viscometer VPZH-2 0.39 EKROS, RUSSIA, Milwaukee MC120 PRO pH Monitor, Electronic stirrer. Analytical scales Sartogosm CE224-S. Preparation of HEC solutions, preparation of HPMC solutions. polymer solutions prepared according to USP standards. Results. The physical characteristics of the obtained mixtures were studied and the compositions of the model mixtures are shown. The solution, which contains benzyl alcohol, ofloxacin as active ingredients and HPMC with 70% ethanol as excipients, is fully meets the requirements of ear drops. Conclusions. Solution, which contains benzyl alcohol, ofloxacin as active ingredients and HPMC with 70% ethanol as excipients, has suitable viscosity and pH, which are fully meets the requirements of ear drops.

Preparation of Various Nanomaterials via Controlled Gelation of a Hydrophilic Polymer Bearing Metal-Coordination Units with Metal Ions.

We investigated the gelation of a hydrophilic polymer with metal-coordination units (HPMC) and metal ions (PdII or AuIII). Gelation proceeded by addition of an HPMC solution in N-methyl-2-pyrrolidone (NMP) to a metal ion aqueous solution. An increase in the composition ratio of the metal-coordination units from 10 mol% to 34 mol% (HPMC-34) increased the cross-linking rate with AuIII. Cross-linking immediately occurred after dropwise addition of an HPMC-34 solution to the AuIII solution, generating the separation between the phases of HPMC-34 and AuIII. The cross-linking of AuIII proceeded from the surface to the inside of the HPMC-34 droplets, affording spherical gels. In contrast, a decrease in the ratio of metal-coordination units from 10 mol% to 4 mol% (HPMC-4) decreased the PdII cross-linking rate. The cross-linking occurred gradually and the gels extended to the bottom of the vessel, forming fibrous gels. On the basis of the mechanism for the formation of gels with different morphologies, the gelation of HPMC-34 and AuIII provided nanosheets via gelation at the interface between the AuIII solution and the HPMC-34 solution. The gelation of HPMC-4 and PdII afforded nanofibers by a facile method, i.e., dropwise addition of the HPMC-4 solution to the PdII solution. These results demonstrated that changing the composition ratio of the metal-coordination units in HPMC can control the gelation behavior, resulting in different types of nanomaterials.

Conception and Clinical Efficacy of an Osmotic, Polymeric, Stable Nasal Filmogen Barrier for Preventive Treatment of Allergen and Pollution Induced Rhinitis and Respiratory Symptoms

Background: Pollution induced allergic rhinitis and respiratory symptoms is becoming a major health problem in the world for which still there is no safe and preventive treatment. Objectives: Conceive and evaluate the allergen preventive properties and clinical efficacy of an osmotic, polymeric, stable filmogen spray, called PCNS. Materials and Methods: Amb A 1 (ragweed), Der P 1 and 2 (dust mite), Bet v 1 (birch), Alt a 1 (Alternaria, fungus), and Fel d 1 (cat dander) allergens were exposed at a concentration of 5µg/ml (20 µl per tube) on the polymeric test product film (120 and 240µl layer) and the allergens crossing the barrier were quantified in the agar gel beneath the film. 0.40% HPMC and PBS solutions, tested identically, served as controls. Clinical efficacy of PCNS nasal spray was evaluated in patients suffering from allergic rhinitis and/or respiratory symptoms (29 in test product v/s 15 in saline controls) for 22 days. Nasal, ocular, respiratory symptoms and Rhino conjunctivitis Quality of Life Questionnaire (RQLQ) were measured. Statistical analyses: The normality of the populations was determined by the Shapiro-Wilk test, then statistical analysis was performed by two-tailed Student’s test for comparisons between two groups and the two-way ANOVA followed by the post hoc Bonferroni’s test for comparisons of multiple groups. p<0.05 was considered statistically significant. The analyses were performed with the software GraphPad Prism (version 8.4.2, La Jolla, USA). NS indicates not significant. Results: PCNS polymeric spray blocked the diffusion of all the allergens while 0.40% HPMC was able to prevent diffusion of only Alt a 1 and Fel d 1 allergens. Mean reflective total nasal symptom scores (rTNSS), reflective total ocular symptom score (rTOSS), and respiratory symptoms including effect on wheezing, cough, dyspnea, and chest tightness were moderately improved in the control saline group, but the improvements were nearly twice better in the PCNS group. RQLQ was improved by 23% in saline spray v/s 46% PCNS group. 4/15 patients in saline group v/s 1/29 in PCNS group required rescue medication during the study. PCNS was highly effective in reducing allergen and pollution induced respiratory symptoms. Conclusion: a polymeric, osmotic, and stable nasal barrier against pollutants and allergens represents an innovative approach against pollution induced respiratory symptoms.

Partitioning of surfactant into drug-rich nanodroplets and its impact on drug thermodynamic activity and droplet size

The excipients present in an amorphous solid dispersion (ASD) are essential functional additives that ultimately influence the drug release performance and absorption. Herein, the effect of a polymer, hypromellose (HPMC), and three chemically diverse surfactants, sodium dodecyl sulfate (SDS), cetyltrimethylammonium bromide (CTAB), and polyoxyethylene sorbitan monooleate (Tween 80, Tween), on the size and stability of the colloidal ketoprofen (KTP)-rich phase generated by liquid-liquid phase separation was evaluated. In addition, the impact of the excipients on the thermodynamic activity of KTP at concentrations in excess of the amorphous solubility was evaluated. Dynamic light scattering measurements showed that using surfactant alone did not effectively suppress coarsening of the KTP-rich phase. In contrast, the combined use of surfactant and HPMC maintained the KTP-rich droplet size at around 200 nm, which was smaller than in HPMC solutions without surfactant. Solution nuclear magnetic resonance spectroscopy revealed that HPMC distributed into the KTP-rich phase, leading to a reduced thermodynamic activity of KTP, and a consequent decrease in the maximum achievable aqueous phase concentration. Moreover, substantial amounts of both CTAB and Tween distributed into the KTP-rich phase from the aqueous phase, while SDS remained predominantly in the aqueous phase. The combined use of HPMC with CTAB or Tween resulted in a further decrease in the thermodynamic activity of KTP relative to in the presence of HPMC alone, due to the mixing of both HPMC and surfactant with the KTP-rich phase. In contrast, the addition of SDS did not reduce the thermodynamic activity of KTP because of the limited distribution of SDS into the KTP-rich phase. A reduction in KTP thermodynamic activity translated to a decreased supersaturation and hence a reduction in the maximum achievable membrane flux. The present study illustrates the complex effects of surfactant and polymer on drug thermodynamic activity, factors which should be considered when optimizing ASD formulations to maximize oral drug absorption. Ideally, excipients that do not substantially impact drug thermodynamic activity should be selected, in particular for drugs where achieving high supersaturation is critical to drive their absorption.

Polymer Type Impacts Amorphous Solubility and Drug-Rich Phase Colloidal Stability: A Mechanistic Study Using Nuclear Magnetic Resonance Spectroscopy.

The polymer used in an amorphous solid dispersion (ASD) formulation plays a critical role in dosage form performance. Herein, drug-polymer interactions in aqueous solution were evaluated in order to better understand the dispersion stability of the colloidal drug-rich phase generated when the amorphous solubility is exceeded. The amorphous solubility (Sa,IBP) of ibuprofen (IBP) decreased when hypromellose (HPMC) or polyvinylpyrrolidone/vinyl acetate (PVP-VA) were present in solution. Solution nuclear magnetic resonance (NMR) spectroscopy revealed that a large amount of HPMC and PVP-VA distributed into the IBP-rich phase. The mixing of HPMC and PVP-VA with the IBP-rich phase led to the decreased Sa,IBP. In contrast, the charged amino methacrylate copolymer (Eudragit E PO, EUD-E) showed minimal mixing with the IBP-rich phase; however, this polymer did lead to solubilization of IBP in the bulk aqueous phase. Although the IBP-rich phase generated by dissolving IBP at concentrations above Sa,IBP rapidly coarsened followed by creaming in the absence of polymer, all of the polymers stabilized the IBP dispersion to some extent. The droplet size of the IBP-rich phase immediately after formation was around 300 nm in HPMC and PVP-VA solutions, and around 800 nm in the EUD-E solution. The mixing of the former two polymers with the drug-rich phase is thought to account for the smaller droplet size. Despite a smaller initial size, the dispersion stability of the IBP-rich droplets was relatively poor in the presence of PVP-VA. In contrast, the coalescence of the IBP-rich droplets was effectively suppressed by the steric repulsion and electrostatic repulsion derived from adsorbed HPMC and EUD-E, respectively. The present study highlights the complex effects of a polymer on the drug amorphous solubility and colloidal stability, which should be considered when optimizing ASD formulations with the goal of maximizing drug absorption.

The influence of viscosity-enhancing agents on oral absorption of drugs.

The objective of this study was to evaluate the influence of viscosity-enhancing agents on oral absorption of metoprolol (MPL) and bisoprolol (BPL). Although the viscosity values were similar for MPL and BPL in hydroxypropyl methylcellulose (HPMC, 1.2 % (w/w)) and polyvinyl alcohol (PVA, 8.8 % (w/w)) solutions, the order of diffusion rate constants of the drugs in media were phosphate buffer solution (reference) > HPMC solution > PVA solution. In in vivo rat intestinal absorption experiments showed that the Cmax and AUC values of the drugs were lowest when they were administered into the rat jejunum in a PVA solution. In vitro binding studies showed that this may have been due to adsorption of the drugs to PVA molecules, resulting in decreased free fractions of the drugs. Our results indicated that intestinal absorption of the drugs in PVA solution was influenced both by decreased diffusion of the drugs and by interaction with PVA. Since various viscosity-enhancing agents are widely used as pharmaceutical and food additives, these findings may be of significance for understanding therapeutic efficacy and safety of oral drug products.

Development of the composition of the tablets "Cardiosten" using the method of mathematical planning of the experiment

The aim of the work is devoted to the substantiation of the choice of excipients while the development of Cardiosten tablets with a dry extract from a mixture of medicinal plant materials of cardiological action, taking into account the application of the mathematical planning of the experiment.Materials and methods. Using the method of mathematical planning of the experiment (MPE), the influence of auxiliary substances on the technological properties of the granules with dry extract “Cardiosten” and tablets obtained from these granules was investigated. Fillers, sorbents (moisture regulators), structure-forming substances (disintegrating agents), binding substances and calcium stearate as a powdering agent (antifriction substance) were used as excipients. All groups of excipients (except calcium stearate) were divided into levels of factors, which were investigated by the four-factor experiment method based on a Greek-Latin square. The following indicators of granules and tablets based on dry extract “Cardiosen” were used as responses: bulk density g/cm3; mass flow for tableting, s/100g; mass loss during wetting and granulation, %; disintegration of tablets, min., abrasion of tablets, % and resistance of tablets to crushing, N.Results. In the course of the conducted research, the dependence of all responses on the above factors was determined according to the technological parameters of the tablet mass and finished tablets.Based on the analysis of the most effective levels of factors that had the maximum effect on the responses, the following substances were selected as further objects: Prosolv HD 90 (vehicle), Neosorb –100 (sorbent), polyplasdon XL10 (structuring agent) and HPMC solution as a binder.Conclusions. Using the MPE method, the most optimal excipients were selected for the production of tablets with a dry extract content of “Cardiosten”. Based on the indicators of pelletized mass (bulk density, bulk flow, weight loss) and tablets (disintegration time of tablets, abrasion of tablets, resistance of tablets to crushing), the qualitative composition of auxiliary substances for the production of tablets by the method of wet granulation - Prosolv HD 90 (filler) was determined , Neosorb – 100 (sorbent), polyplasdon XL10 (structuring agent), HPMC solution (binding agent).

Kinetics of immersion nucleation driven by surface tension

Immersion nucleation is the nuclei formation mechanism for wet granulation systems where the liquid drops are large relative to the primary particles. The process of immersion nucleation has been examined in many studies, however the kinetics of nuclei formation are not well understood, and there is a distinct lack of experimentally validated models for this process.A kinetic model has been proposed by Hounslow et al. (2009) which describes surface tension driven immersion nucleation. This paper presents the results from a series of experiments measuring the kinetics of immersion nucleation, and these results are compared with the model predictions. Drops of model liquids (aqueous HPMC solution and silicone oil) are placed on static powder beds of zeolite and lactose. Nuclei granules are carefully excavated at different times and the change in granule mass with time is measured. As predicted by Hounslow et al.'s model, the granule mass increases with the square root of time to a maximum granule size at a time tmax after an initial adjustment period. The critical packing factor is shown to be a function of powder properties, and not dependent on the liquid properties. The model captures well the measured effects of liquid and powder properties. However, the kinetics of the nucleation process are much slower than predicted by the model. It is believed this is due to continued percolation of the liquid within the powder bed, after the liquid drop is fully immersed. This secondary liquid movement may have an important effect on granule growth kinetics, and influence final granule product properties.

Morphological and Physicochemical Evaluation of Two Distinct Glibenclamide/Hypromellose Amorphous Nanoparticles Prepared by the Antisolvent Method.

The morphology and stability of amorphous nanoparticles of glibenclamide (GLB) prepared by the antisolvent method using different methods of adding hypromellose (HPMC) were evaluated. Nano-A was prepared by the injection of a dimethyl sulfoxide (DMSO) solution of GLB into the HPMC solution, whereas nano-B was obtained by the injection of a DMSO solution of GLB and HPMC into water. Cryogenic transmission electron microscopy, field-emission scanning electron microscopy, and field-emission transmission electron microscopy, including energy dispersive X-ray spectrometry, revealed that the particles of the nano-A and nano-B samples are hollow spheres and nonspherical nanoparticles, respectively. Powder X-ray diffraction and solid-state NMR measurements showed that GLB is present in an amorphous state in both nano-A and nano-B. The weight ratios of HPMC in the GLB/HPMC nanoparticles were 11 and 16% for nano-A and nano-B, respectively, as determined by solution-state NMR. The glass transition temperatures ( Tg) of nano-A and nano-B evaluated using differential scanning calorimetry were lower by about 10 °C compared to that of amorphous GLB, presumably because of a Tg confinement effect and the surface coverage and mixing of HPMC, as suggested by the inverse gas chromatography experiment. GLB crystallization during storage was suppressed more strongly in nano-B than nano-A, owing to the higher amount of HPMC and the higher miscibility between GLB and HPMC. It is suggested that the diffusion rate of the solvent during nanoprecipitation determined the nanoparticle properties. In nano-A, the precipitation of GLB first occurred at the outer interface because of the rapid diffusion of the solvent. Thus, hollow spherical particles with HPMC preferentially located near the surface were formed. On the other hand, the diffusion of the solvent in nano-B was suppressed because of the presence of HPMC, yielding small nonspherical nanoparticles with a high miscibility of GLB and HPMC.

Optimisation of HPMC ophthalmic inserts with sustained release properties as a carrier for thermolabile therapeutics

A methodology was developed and optimised for the preparation of a new drug delivery system (DDS) with sustained release properties to allow ocular protein delivery and to limit destructive production steps during manufacturing. Elevated temperatures, shear forces and an oxidative environment should be avoided in order to prevent denaturation or oxidation of proteins. An aqueous HPMC solution was prepared using heat and casted into small semi-rod-shaped PVC blisters. The polymer solution was allowed to cool down and was partially dehydrated at room temperature. A drug solution containing glycerol, drug and water was subsequently added to rehydrate the partially dehydrated polymer matrix at a temperature of 2°C. Several parameters of the production process were varied to determine their influence on the release kinetics from HPMC inserts from three different molecules of different molecular weight. This production method was further optimised in order to shorten the rehydration time from weeks to days, while eliminating heat and shear forces on the selected drug molecules sodium fluorescein, lysozyme and albumin. Slow release kinetics were achieved for sodium fluorescein and lysozyme as model drug molecules. The higher molecular weight of albumin prevented a good penetration into the insert during the rehydration process resulting in predominantly burst release. The biocompatibility of a viscous HPMC solution was evaluated on SV40-human corneal epithelial cells with PrestoBlue® and no cytotoxic effects were observed.

Design and optimization of thermosensitive nanoemulsion hydrogel for sustained-release of praziquantel

Objective: This work aimed to develop an alternative sustained-release thermosensitive praziquantel-loaded nanoemulsion (PZQ-NE) hydrogel for better schistosomiasis treatment.Significance: PZQ-NE-dispersed chitosan/glycerol 2-phosphate disodium/HPMC (NE/CS/β-GP/HMPC) hydrogel was successfully prepared to improve bioavailability of PZQ.Methods: Solubility tests and pseudo-ternary phase diagrams were applied to screen optimal oils, surfactants and co-surfactants of NE. The hydrogels were characterized for gelling time, surface exudates, rheological properties and in vitro drug release. Formulation optimization of NE/CS/β-GP/HMPC hydrogel was conducted by Box–Behnken experimental design combined with response surface methodology. In vitro cytotoxicity of hydrogel was studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide method. The sustained-release property of PZQ in NE and optimized hydrogel was evaluated by pharmacokinetic study in rabbits.Results: The formulation of PZQ-NE consisted of mass ratio of 12.5% capryol 90 containing PZQ (160 mg/g), 40% cremophor RH 40/tween 20 and transcutol HP (S/CoS = 2:1), 47.5% deionized water. PZQ releasing from NE/CS/β-GP/HMPC hydrogels was best fitted to Higuchi model and governed by diffusion. Rheological investigation evidenced the themosensitive gelation of different hydrogel systems and their gel-like character at 37 °C. The optimized hydrogel formulation consisted of HPMC solution (103.69 mg/g), 3.03% (w/v) chitosan and 14.1% (w/v) β-GP showed no cytotoxicity when the addition of NE was no more than 100 mg/g. Pharmacokinetic parameters indicated that NE/CS/β-GP/HMPC hydrogel can significantly slow down drug elimination, prolong mean residence time and improve bioavailability of PZQ.Conclusions: NE/CS/β-GP/HMPC hydrogel possessed sustained-release property and could be an alternative antischistosomal drug delivery system with improved therapeutic effect.

Preparation and Evaluation of Stomatitis Film Using Xyloglucan Containing Loperamide.

Stomatitis induced by radiation therapy or cancer chemotherapy is a factor in sleep disorders and/or eating disorders, markedly decreasing patient quality of life. In recent years, disintegrating oral films that are easy to handle have been developed; therefore, we focused on the formulation of these films. We prepared an adhesive film for the oral cavity using xyloglucan (Xylo), which is a water-soluble macromolecule. We used loperamide, which has been reported to relieve pain caused by stomatitis effectively, as a model drug in this study. Films were prepared from Xylo solutions (3% (w/w)) and hypromellose (HPMC) solutions (1% (w/w)). Xylo and HPMC solutions were mixed at ratios of 1 : 1, 2 : 1, or 3 : 1 for each film, and films 2×2 cm weighing 3 g were prepared and dried at 37°C for 24 h. Physicochemical properties such as strength, adhesiveness, disintegration behavior, and dissolution of loperamide from films were evaluated. Films prepared from Xylo solution alone had sufficient strength and mucosal adhesion. On the other hand, films prepared from a mixture of Xylo and HPMC were inferior to those made from Xylo, but showed sufficient strength and mucosal adhesion and were flexible and easy to handle. The films prepared in this study are useful as adhesion films in the oral cavity.

An Insight into Different Stabilization Mechanisms of Phenytoin Derivatives Supersaturation by HPMC and PVP

In this study, we examined the stabilization mechanism of drug supersaturation by hypromellose (HPMC) and polyvinylpirrolidone (PVP). The poorly water-soluble drugs, phenytoin (diphenylhydantoin, DPH), and its synthesized derivatives monomethylphenytoin (MDPH) and dimethylphenytoin (DMDPH) were used. DPH supersaturation was efficiently maintained by both HPMC and PVP. HPMC maintained the supersaturation of MDPH and DMDPH in a similar manner to that of DPH, whereas the ability of PVP to maintain drug supersaturation increased as follows: DPH>MDPH>DMDPH. Caco-2 permeation studies and nuclear magnetic resonance measurements revealed that the permeability and molecular state of the drug in a HPMC solution barely changed. In fact, the solubilization of the drug into PVP changed its apparent permeability and molecular state. The drug solubilization efficiency by PVP was higher and followed the order: DPH>MDPH>DMDPH. The different drug solubilization efficiencies most likely result from the different strengths in the intermolecular interaction between the DPH derivatives and PVP. The difference in the stabilization mechanism of drug supersaturation by HPMC and PVP could determine whether the efficient maintenance of the drug supersaturation was dependent on the drug species. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:2574–2582, 2015

Novel use of superdisintegrants as viscosity enhancing agents in biocompatible polymer films containing griseofulvin nanoparticles

The advantages of using superdisintegrants, sodium starch glycolate (SSG), croscarmellose sodium (CCS) and crospovidone (CP) over traditional high molecular weight (MW) viscosity enhancing agents, guar gum (GG), xanthan gum (XG), pectin and high MW HPMC are examined for improving drug content uniformity without compromising dissolution of films containing nanoparticles of griseofulvin (GF), used as a model poorly water-soluble drug. Films were fabricated by preparing low MW HPMC solutions to which a fixed amount of viscosity enhancing agents was added and mixed with GF nanosuspensions produced via wet milling, followed by casting and drying. The addition of superdisintegrants and high MW HPMC led to an increase in viscosity of precursor suspensions without GF particle aggregation, and hence excellent drug content uniformity along with retention of the high surface area of the GF nanoparticles in dried films. In contrast, the addition of XG and pectin resulted in aggregation of GF particles in suspensions, leading to poor content uniformity and incomplete recovery of GF nanoparticles upon redispersion of dried films. In spite of their high precursor viscosity, the films containing superdisintegrants did not lead to increased mechanical strength and demonstrated fast drug release, suggesting faster matrix erosion. In contrast, films with high MW polymers (GG, XG, and pectin and high MW HPMC) had increased mechanical strength and their subsequent slow erosion/disintegration along with longer hydration times resulted in significant delay of drug release, which was found to be directly proportional to their MW. These results demonstrate novel use for superdisintegrants as economical and superior alternative to traditional viscosity enhancing agents in forming drug laden biocompatible polymer films.

Evaluation of a newly developed HPMC ophthalmic insert with sustainehttp://10.10.23.106:8080/TDXPSLIVEGANG/gateway/elsevierjournal/index.jsp#d release properties as a carrier for thermolabile therapeutics

A novel drug delivery system (DDS) with sustained release properties was developed to allow ocular protein delivery. The DDS developed is aimed at overcoming stability issues during preparation such as denaturation of proteins caused by shear forces applied or due to elevated temperatures and air entrapment potentially causing oxidation of the molecule. The rod-shaped HPMC inserts were loaded with lysozyme and several HPMC types were studied and compared. An aqueous colloidal HPMC solution (hydrogel) was prepared and subsequently dried at 150°C to dehydrate the polymer solution. This partially dehydrated polymer cylinder was loaded with an aqueous glycerol/lysozyme solution at 2°C. A 24 full factorial design was set up to evaluate the effect of the different preparation parameters on water uptake and release properties. As a result, four out of sixteen formulations revealed homogenous distribution for lysozyme in both duplicates. The change in water uptake over time was dependent on the type of HPMC polymer used but not between the chosen HPMC percentages. After 240min, 50% of lysozyme loaded was released depending on the chosen formulation. Lysozyme molecules exhibit slower release from a K100M matrix compared to E10M inserts, albeit the overall effect is relatively limited.

Formulation, Physicochemical Characterization, and In Vitro Study of Chitosan/HPMC Blends-Based Herbal Blended Patches

The current work prepared chitosan/hydroxypropyl methylcellulose (HPMC) blends and studied the possibility of chitosan/HPMC blended patches for Zingiber cassumunar Roxb. The blended patches without/with crude Z. cassumunar oil were prepared by homogeneously mixing the 3.5% w/v of chitosan solution and 20% w/v of HPMC solution, and glycerine was used as plasticizer. Then, they were poured into Petri dish and produced the blended patches in hot air oven at 70 ± 2°C. The blended patches were tested and evaluated by the physicochemical properties: moisture uptake, swelling ratio, erosion, porosity, Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction, and photographed the surface and cross-section morphology under SEM technique. Herbal blended patches were studied by the in vitro release and skin permeation of active compound D. The blended patches could absorb the moisture and became hydrated patches that occurred during the swelling of blended patches. They were eroded and increased by the number of porous channels to pass through out for active compound D. In addition, the blended patches indicated the compatibility of the blended ingredients and homogeneous smooth and compact. The blended patches made from chitosan/HPMC blends provide a controlled release and skin permeation behavior of compound D. Thus, the blended patches could be suitably used for herbal medicine application.

Nitrofurantoin enteric pellets with high bioavailability based on aciform crystalline formation by wet milling

The aim of the present study was to grind nitrofurantoin (NF) with HPMC solution and to determine the dissolution and bioavailability of the enteric pellets prepared with the NF cogrounds and other excipients. During milling, crystalline transformation occurred – the aciform microcrystalline monohydrate II replaced the coarse crystal anhydrate β and the particle size markedly reduced. In vitro test demonstrated that the enteric pellets prepared with NF cogrounds (4 h) revealed a faster dissolution than the commercial tablet and 50% was released within 30 min in the basic medium. Finally, an in vivo test was conducted in beagle dogs. The Cmax and AUC(0→24) of the pellets were 2.19 ± 0.74 μg/ml and 6.73 ± 4.71 μg/ml h, respectively, while the corresponding values were 0.49 ± 0.42 μg/ml and 1.38 ± 1.17 μg/ml h for the tablet. Thus, the bioavailability of the pellets was increased significantly. In conclusion, the wet grinding that reduced the particle size and created the microcrystalline played a major role in the acceleration of the dissolution of NF and, consequently, enhanced the bioavailability, and the wet grinding process offers an alternative approach to improve the dissolution and bioavailability of drugs with poor aqueous solubility.

Sustained-release pellets of nifedipine using microcrystals combined with MCC-based matrix

The purpose of this study was to prepare sustained-release pellets of nifedipine (NSPs) based on MCC matrix. Wet-milling and extrusion-spheronization techniques were employed to prepare the microcrystals and pellets, respectively. The drug release mechanism and the influencing factors were investigated. After milled with HPMC (E5), the mean particle size of nifedipine in co-grinding mixture (CGM) was 5 μm, which is 15-fold smaller than that of raw material. DSC, X-ray powder diffraction and microscopic observation confirmed the microcrystals of drug were maintained in the CGM. With increased milling time and the content of HPMC, the dissolution rate was greatly enhanced compared with the raw material. The NSPs prepared by MCC and the CGM, which was obtained by cogrinding nifedipine with 5% HPMC solution for 210 min, exhibited sustained release pattern within 8 h. Nifedipine release from MCC-based NSPs followed the Korsmeyer model and closely related to the microstructure of pellet. High stability of NSPs was confirmed after 6 months of accelerated stability test. Using commercially available sustained product as reference, bioequivalence study in beagle dogs was executed and two formulations were bioequivalent. This sustained release pellet formulation of nifedipine was advantageous with convenient and easy scaled-up preparation process.

Effects of Concentration and Temperature on Rheological Properties of Mixture of HPMC and CMC Solutions

This work was designed to study the rheologicl properties of mixture of HPMC and CMC solutions because their rheologicl properties are very important in no matter food or pharmaceutical industry processing operations. Experiments were performed at different mixture ratios, shear rates and temperatures. The static and dynamic rheological properties tests were measured through the rheometer AR-550 and were investigated by using Power Law equation, Cross equation and Arrhenius equation. The results showed that the HPMC-CMC solutions behaved as typical Non-Newtonian shear-thinning fluids and had stronger non-Newtonian nature. With the concentration(CMC)increasing, consistency coefficient K, Zero Shearing Viscosity η0,viscous flow activation energy E, storage modulus G and loss modulus G all increased but decreased with the temperature increasing, except for Non-Newtonian index n. And viscosity was the dominant property in the mixture of HPMC-CMC solutions.