SciCombinator

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Concept: Hypromellose

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The present investigation was carried out to formulate and optimize the bioerodable insert of Azithromycin in order to prolong the release time and improve the ocular availability in ophthalmic infections. A modified solvent casting method was used for the preparation of azithromycin insert in which hydroxyl propyl methyl cellulose (HPMC) and Eudragit RL100 were used as drug reservoir and rate controlling membrane respectively. Thereafter the, formulations were evaluated for the uniformity of thickness and weight, surface pH, folding endurance, percentage moisture loss, percentage moisture absorption, drug content, in-vitro release, kinetics studies (zero order, first order, Higuchi and Korsmeyer - Peppas model) and stability studies. The Formulation H8 (amongst the range of H1-H10) ,comprising of 1.5% HPMC and 3% Eudragit RL100 ,was found to be optimized formulation on the basis of uniformity of thickness (0.26 ± 0.004 mm) and weight (24.9 ± 0.27 mg), surface pH (7.1 ± 0.063), folding endurance (18.3 ± 0.81), percentage moisture loss (7.49 ± 0.30%), percentage moisture absorption (5.7%), drug content (1.98 mg ), in-vitro release (99%) , stability studies (Shelf life- 346 days) and better ocular tolerability. The formulation H8 showed a steady and controlled release of the drug over a 12 hour period with non-Fickian diffusion release mechanism, compared to a normal release period of 2-3 hours. The optimized insert showed promising results and can be used to treat a wide range of ocular infections.

Concepts: Pharmaceutical formulation, Hypromellose, Shelf life, Formulation, Control, E number, Methyl cellulose, Cellulose

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The objective of this study was to investigate the effect of polymeric microcarriers on the in-vivo intranasal uptake of an anti-migraine drug for brain targeting. Mucoadhesive powder formulations consisted of antimigraine drug, zolmitriptan, and chitosans (various molecular weights and types) or hydroxypropyl methylcellulose (HPMC). Their suitability for nasal administration was evaluated by in-vitro and ex-vivo mucoadhesion and permeation tests. The formulations based on chitosan glutamate (CG) or HPMC were tested in-vivo because they showed good mucoadhesive properties and altered the permeation rate of the drug. The in-vivo results from intravenous infusion and nasal aqueous suspension of the drug or nasal particulate powders were compared. The plasmatic AUC values obtained within 8 h following intravenous administration appeared about three times higher than those obtained by nasal administration, independent of the formulations. Zolmitriptan concentrations in the cerebrospinal fluid obtained from nasal and intravenous administrations were respectively 30 and 90 times lower than the concentrations of the drug in the blood. Thus, nasal administration potentiated the central zolmitriptan activity allowing a reduction of the drug peripheral levels, with respect to the intravenous administration. Among nasally administered formulations, CG microparticles showed the highest efficacy in promoting the central uptake of zolmitriptan within 1 h.

Concepts: Psychoactive drug, Hypromellose, Methyl cellulose, Route of administration, Cerebrospinal fluid, Bolus, Intravenous therapy, Chemistry

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Several beneficial effects on the skin have been reported for coumestrol (COU), such as protection against photoaging and improvement of skin elasticity and thickness in postmenopausal women. However no reports on the effect of COU on wound healing were found. Nevertheless, COU has low aqueous solubility, which is a crucial limitation for biological tests. The present study was designed as a two-step experiment to evaluate the wound healing effect of COU. First, we used fibroblasts and the experimental in vitro artificial wound model, scratch assay, to compare the effects of COU free, dissolved in dimethyl sulfoxide (DMSO) or Dulbecco’s modified Eagle’s medium (DMEM), or associated with hydroxypropyl-β-cyclodextrin (HPβCD). The 50 μM (66.1%) and 10 μM (56.3%) COU/HPβCD association induced cell proliferation and migration in inflicted wounds. Subsequently, the in vivo wound healing experimental model (Wistar rats) revealed that COU/HPβCD incorporated into hypromellose (HPMC) hydrogel had similar efficacy in wound healing in comparison to the positive control (Dersani®), with the advantage that 50% wound healing was achieved within a shorter period. In summary, the results successfully demonstrated, for the first time, the wound healing effect of COU/HPβCD incorporated into HPMC hydrogel and describe the feasibility of the biological tests with the use of HPβCD instead DMSO.

Concepts: Dimethyl sulfide, Effectiveness, Healing, In vitro, Methyl cellulose, Hypromellose, In vivo, Wound healing

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In line with the increasing demand for sustainable packaging materials, this contribution aimed to investigate the film-forming properties of hydroxypropyl methylcellulose (HPMC) to correlate its chemical structure with film properties. The roles played by substitution degree (SD) and molecular weight (Mw) on the mechanical and water barrier properties of HPMC films were elucidated. Rheological, thermal, and structural experiments supported such correlations. SD was shown to markedly affect film affinity and barrier to moisture, glass transition, resistance, and extensibility, as hydroxyl substitution lessens the occurrence of polar groups. Mwaffected mostly the rheological and mechanical properties of HPMC-based materials. Methocel®E4 M led to films featuring the greatest tensile strength (ca., 67 MPa), stiffness (ca., 1.8 GPa), and extensibility (ca., 17%) and the lowest permeability to water vapor (ca., 0.9 g mm kPa-1 h-1 m-2). These properties, which arise from its longer and less polar chains, are desirable for food packaging materials.

Concepts: Hypromellose, Methyl cellulose, Sustainable packaging, Packaging and labeling, Water, Chemistry, Molecule, Packaging

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This study aimed to develop novel co-processed tablet fillers based on the principle of particle engineering for direct compaction and to compare the characteristics of co-processed products obtained by fluid-bed coating and co-spray drying, respectively. Water-soluble mannitol and water-insoluble calcium carbonate were selected as representative fillers for this study. Hydroxypropyl methylcellulose (HPMC), serving as a surface property modifier, was distributed on the surface of primary filler particles via the two co-processing methods. Both fundamental and functional properties of the products were comparatively investigated. The results showed that functional properties of the fillers, like flowability, compactibility, and drug-loading capacity, were effectively improved by both co-processing methods. However, fluid-bed coating showed greater advantages over co-spray drying in some aspects, which was mainly attributed to the remarkable differences in some fundamental properties of co-processed powders, like particle size, surface topology, and particle structure. For example, the more irregular surface and porous structure induced by fluid-bed coating could contribute to better compaction properties and lower lubricant sensitivity due to the increasing contact area and mechanical interlocking between particles under pressure. More effective surface distribution of HPMC during fluid-bed coating was also a contributor. In addition, such a porous agglomerate structure could also reduce the separation of drug and excipients after mixing, resulting in the improvement in drug loading capacity and tablet uniformity. In summary, fluid-bed coating appears to be more promising for co-processing than spray drying in some aspects, and co-processed excipients produced by it have a great prospect for further investigations and development.

Concepts: E number, Pharmacology, Calcium carbonate, Hypromellose, Methyl cellulose, Better, Tablet, Excipients

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In spite of significant recent interest in polymeric films containing poorly water-soluble drugs, dissolution mechanism of thicker films has not been investigated. Consequently, release mechanisms of poorly water-soluble drugs from thicker hydroxypropyl methylcellulose (HPMC) films are investigated, including assessing thickness above which they exhibit zero-order drug release. Micronized, surface modified particles of griseofulvin, a model drug of BSC class II, were incorporated into aqueous slurry-cast films of different thicknesses (100, 500, 1000, 1500 and 2000 μm). Films 1000 μm and thicker were formed by either stacking two or more layers of ~500 μm, or forming a monolithic thick film. Compared to monolithic thick films, stacked films required simpler manufacturing process (easier casting, short drying time) and resulted in better critical quality attributes (appearance, uniformity of thickness and drug per unit area). Both the film forming approaches exhibited similar release profiles and followed the semi-empirical power law. As thickness increased from 100 μm to 2000 μm, the release mechanism changed from Fickian diffusion to zero-order release for films ≥1000 μm. The diffusional power law exponent, n, achieved value of 1, confirming zero-order release, whereas the percentage drug release varied linearly with sample surface area, and sample thickness due to fixed sample diameter. Thus, multi-layer hydrophilic polymer aqueous slurry-cast thick films containing poorly water-soluble drug particles provide a convenient dosage form capable of zero-order drug release with release time modulated through number of layers.

Concepts: Drug addiction, Pharmacology, Solubility, Drugs, Drug, Hypromellose, E number, Methyl cellulose

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Due to its versatile properties, hydroxypropyl methylcellulose (HPMC) is largely used in many applications and deeply studied in the various fields such as pharmaceuticals, biomaterials, agriculture, food, water purification. In this work, vitamin B12 loaded HPMC granules were produced to investigate their potential application as nutraceutical products. To this aim the impact of vitamin load on physico-chemical, mechanical and release properties of granules, achieved by wet granulation process, was investigated. In particular, three different loads of B12 (1%, 2.3% and 5% w/w) were assayed. Unloaded granules (used as control) and loaded granules were dried, sieved, and then the suitable fraction for practical uses, 0.45-2mm in size, was fully characterized. Results showed that the vitamin incorporation of 5% reduced the granulation performance in the range size of 0.45-2mm and led granules with higher porosity, more rigid and less elastic structures compared to unloaded granules and those loaded at 1% and 2.3% of B12. Vitamin release kinetics of fresh and aged granules were roughly found the same trends for all the prepared lots; however, the vitamin B12 was released more slowly when added with a load at 1% w/w, suggesting a better incorporation.

Concepts: E number, Cofactor, Hypromellose, Materials science, Vitamin, Methyl cellulose, Vitamin B12, Folic acid

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Solid oral dosage forms (SODF) are drug vehicles commonly prescribed by physicists in primary and secondary cares, as they are the most convenient for the patient and facilitate therapy management. Concerns regarding unintended adhesion of SODF during oro-esophageal transit remain, especially in multimorbid patients, bedridden patients and patients suffering from dysphagia. Hence, this factor should be considered during the development of SODF, and more attention should be given on the design of appropriate surface conditions considering patients with swallowing problems. The aim of this work was to estimate the low mucoadhesion strength of different pharmaceutical polymers frequently used in coating technologies, since this property is thought to have impact on the mucoadhesive profile of SODF during oro-esophageal transit. In an approach using in vitro methods based on particle interactions, polyethylene glycol grades (PEG) showed the lowest interaction forces suggesting a more favorable in vivo performance than hydroxypropyl methylcellulose (HPMC), which was found to have the highest particle interaction. Preference should be given to coating formulations with lower concentrations of polymer and grades with low molecular weight. In addition, rheological measurements should be adopted when targeting poor mucoadhesive polymers.

Concepts: Hypromellose, Polymer, Patient, Polymers, Methyl cellulose, In vivo, In vitro, Pharmacology

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This study aimed to compare the dissolution and the intestinal absorption of tacrolimus in self-microemulsifying drug delivery system (SMEDDS) and solid dispersion (SD). Poloxamer 188 SD was prepared by the combination of the solvent evaporation method and the freeze drying method. Hydroxypropyl methylcellulose (HPMC) SD was prepared by the solvent evaporation method combined with the vacuum drying method. The formation of SD was confirmed by SEM images which showed new solid phases. The SMEDDS was composed of oil (Labrafil M1944 CS 28%), surfactant (Cremophor EL 48%) and co-surfactant (Transcutol P 24%). The self microemulsion formed by the SMEDDS upon aqueous media had spherical droplets with a hydrodynamic size of 46.0±3.2nm. The dissolution of tacrolimus from SD and SMEDDS was performed in sink and non-sink conditions with various pH. As revealed by the DSC and FT-IR, the tacrolimus was molecularly or amorphously dispersed in the SMEDDS and SD. The in vivo intestinal absorption study in rats showed that both SMEDDS and SD improved the absorption of tacrolimus over the raw tacrolimus while the SMEDDS exhibited lower absorption rate constant (Ka) and apparent permeability coefficients (Papp) than the SD. The self-prepared SD with poloxamer 188 or HPMC had comparable intestinal absorption as compared with Prograf®. The tacrolimus-loaded SMEDDS and SD would be further compared by in vivo pharmacokinetic study.

Concepts: Food preservation, Freeze drying, Emulsion, Hypromellose, Pharmacology, Methyl cellulose, Cellulose, Liquid

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This study presents a design that lipophilic drug was encapsulated within dissolving microneedles (DMNs) for sustained-release delivery over one week. Etonogestrel (ENG), the progestogen used in hormonal contraceptives, was loaded in two-layered DMNs in form of microcrystal particles (MP). In vitro release study indicated that ENG in form of MP could sustain drug release compared to non-crystal form. Hydroxypropyl methylcellulose (HPMC) and polyvinyl alcohol (PVA) was used to prepare the fast dissolving needle-tips and flexible back layer, respectively. The mechanical strength of microneedles was not affected even with the drug loading efficiency of 50.0% in needle-tips. The penetration depth of DMNs in skin, observed by confocal laser scanning microscopy (CLSM), was approximately 280 μm. The tips of DMNs could be dissolved in rat skin within 1 hour with drug delivery efficiency of 63.8 ±2.0%. Pharmacokinetics study of DMNs treatment in rats showed that the plasma levels of ENG were a dose-dependent profile and much steadier than intradermal injection. There was no statistical difference between bioavailability of ENG treated by DMNs or intradermal injection (p > 0.05). Therefore, the novel DMNs loaded with drug MP provided a potential minimally invasive route for intradermal sustained delivery of lipophilic drug.

Concepts: Implanon, Hypromellose, Hormonal contraception, Methyl cellulose, Pharmaceutical drug, Polyvinyl acetate, Polyvinyl alcohol, Pharmacology