Grades Of Hydroxypropyl Methylcellulose Research Articles

Studying the API Distribution of Controlled Release Formulations Produced via Continuous Twin-Screw Wet Granulation: Influence of Matrix Former, Filler and Process Parameters.

Hydroxypropyl methylcellulose (HPMC) is a preferred hydrophilic matrix former for controlled release formulations produced through continuous twin-screw wet granulation. However, a non-homogeneous API distribution over sieve fractions with underdosing in the fines fraction (<150 µm) was previously reported. This could result in content uniformity issues during downstream processing. Therefore, the current study investigated the root cause of the non-homogeneous theophylline distribution. The effect of process parameters (L/S-ratio and screw configuration) and formulation parameters (matrix former and filler type) on content uniformity was studied. Next, the influence of the formulation parameters on tableting and dissolution behavior was investigated. Altering the L/S-ratio or using a more aggressive screw configuration did not result in a homogeneous API distribution over the granule sieve fractions. Using microcrystalline cellulose (MCC) as filler improved the API distribution due to its similar behavior as HPMC. As excluding HPMC or including a hydrophobic matrix former (Kollidon SR) yielded granules with a homogeneous API distribution, HPMC was identified as the root cause of the non-homogeneous API distribution. This was linked to its fast hydration and swelling (irrespective of the HPMC grade) upon addition of the granulation liquid.

Controlled Release Bilayer Floating Effervescent and Noneffervescent Tablets Containing Levofloxacin and Famotidine

The present study is aimed at designing bilayer-floating tablets to improve the drug concentration in the stomach for enhanced therapeutic efficacy. The tablets are comprised of an upper layer of levofloxacin (466.5 mg) and a lower layer of famotidine (133.5 mg). Five formulations (F1-F5) were developed by using hydroxypropyl methylcellulose grades (K4M, K15M, and K100M) along with Carbopol 934. In the case of the effervescent system (F1-F3), sodium bicarbonate was added to impart buoyancy to the tablets; while in the case of noneffervescent formulations (F4 &amp; F5), guar gum and xanthan gum were incorporated to induce flotation and swelling and retard the release of a drug. The precompression characteristics of tablets depict the suitability of all formulation powder for direct compression. The ATR-FTIR analyses have shown that the components of both effervescent and noneffervescent tablets are compatible with each other. The total weight of each tablet was 600 mg, with a weight variation of about ≤10 mg. Both the layers were smooth and flat with a thickness ranging from 3.16±0.04 to 3.54±0.01 mm. The diameters of prepared floating tablets were about 15 mm, optimum for oral administration. After adjusting the tablet’s hardness to 6-7 kg/cm2, its friability was found to be &lt;0.35 percent. The mean drug content of the formulations was above 90%. The floating lag time of all formulations (F2-F5) was below 25 seconds, except F1 which took almost 50 seconds to start floating on the surface of gastric content due to its higher density. The total floating time of effervescent (F1-F3) and noneffervescent formulations was in the range of 15-25 hours, thereby providing sufficient time to complete drug release and absorption in the gastric area. The total floating time of noneffervescent formulations was higher (p≤0.05) than effervescent formulations due to efficient wettability and swelling characteristics. The release of drugs from both layers of noneffervescent tablets was significantly controlled when compared to the effervescent system, and an anomalous non-Fickian diffusion was found for the drug release. The stability study of the optimized formulation proved the integrity and stability of the developed formulation. Thus, developed formulations are deemed suitable for controlled codelivery of active pharmaceutical ingredients for the effective treatment of H. pylori.

Impact of drug load and polymer molecular weight on the 3D microstructure of printed tablets

This study investigates the influence of drug load and polymer molecular weight on the structure of tablets three-dimensionally (3D) printed from the binary mixture of prednisolone and hydroxypropyl methylcellulose (HPMC). Three different HPMC grades, (AFFINISOLTM HPMC HME 15LV, 90 Da (HPMC 15LV); 100LV, 180 Da (HPMC 100LV); 4M, 500 Da (HPMC 4M)), which are suitable for hot-melt extrusion (HME), were used in this study. HME was used to fabricate feedstock material, i.e., filaments, at the lowest possible extrusion temperature. Filaments of the three HPMC grades were prepared to contain 2.5, 5, 10 and 20 % (w/w) prednisolone. The thermal degradation of the filaments was studied with thermogravimetric analysis, while solid-state properties of the drug-loaded filaments were assessed with the use of X-ray powder diffraction. Prednisolone in the freshly extruded filaments was determined to be amorphous for drug loads up to 10%. It remained physically stable for at least 6 months of storage, except for the filament containing 10% drug with HPMC 15LV, where recrystallization of prednisolone was detected.Fused deposition modeling was utilized to print honeycomb-shaped tablets from the HME filaments of HPMC 15LV and 100LV. The structural characteristics of the tablets were evaluated using X-ray microcomputed tomography, specifically porosity and size of structural elements were investigated. The tablets printed from HPMC 15LV possessed in general lower total porosity and pores of smaller size than tablets printed from the HPMC 100LV. The studied drug loads were shown to have minor effect on the total porosity of the tablets, though the lower the drug load was, the higher the variance of porosity along the height of the tablet was observed. It was found that tablets printed with HPMC 15LV showed higher structural similarity with the virtually designed model than tablets printed from HPMC 100LV. These findings highlight the relevance of the drug load and polymer molecular weight on the microstructure and structural properties of 3D printed tablets.

Development and Evaluation of Buccal Mucoadhesive patches of Losartan Potassium

Buccal mucoadhesive patches of losartan potassium were formulated using hydroxypropyl methyl cellulose grades - K4M, K15M, K50M and Eudragit L100 polymers by the method of solvent casting. The prepared formulations were characterized for mechanical and physicochemical parameters like thickness, surface pH, uniformity of weight, swelling index, folding endurance, percentage moisture loss, drug content, in vitro dispersion and in vitro residence time. Further, in vitro drug release study was performed with the use of freshly prepared egg membrane as the semi-permeable membrane. The best formulation (F6) exhibited higher percentage of drug release 97.26%±0.41 at the end of 8 h. The sustained release of losartan potassium was found to be attained up to 8 h duration.

In vivo Evaluation of Solid dispersion of Glipizide with Low Viscosity Grade Hydroxypropyl Methylcellulose

The aim of this study was to make and characterize Glipizide solid dispersions utilizing a low viscosity grade of hydoxypropyl methyl cellulose (HPMCLV). The phase solubility character of Glipizide in presence of various concentrations of HPMCLV in 0.1N HCl was evaluated. Glipizide solubility increases as the concentration of HPMC in 0.1N HCl was increased. Gibbs free energy (ΔGotr) values were all negative, indicating that drug solubilization occurs spontaneously. Solid dispersions of Glipizide with HPMCLV were prepared by using solvent evaporation method The physical properties of Glipizide with HPMCLV SDs were investigated using Fourier-transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction (XRD). Dissolution studies was also performed. Subsequently, bioavailability of pure Glipizide, solid dispersion and marketed product was performed. Glipizide dissolution rate was enhanced in SDs containing HPMC, and the rate increased as the concentration of HPMC in the SDs increase. After preparing SDs and a physical mixture with HPMC, the mean dissolving time (MDT) of Glipizide decreased significantly. FTIR spectroscopy tests revealed Glipizide's stability and the absence of a well-defined Glipizide-HPMCLV interaction. The amorphous condition of Glipizide in SDs of Glipizide with HPMCLV was revealed by DSC and XRD studies. When compared to pure drug and marketed product, solid dispersion of Glipizide with HPMCLV exhibited improved bioavailability.

Development and characterization of bimodal chrono modulated drug delivery of methylphenidate hydrochloride

The study's goal was to develop chrono modulated pulsatile tablets of methylphenidate hydrochloride with an extended-release pattern in the morning and an immediate burst release in the afternoon for exaggerated symptoms of attention deficit hyperactivity disorder match the circadian rhythm of disease, where high levels of l-3, 4-dihydroxyphenylalanine (DOPA) are observed in the afternoon, necessitating higher drug concentrations. The core tablets were made with Kollidon CL-SF as a super disintegrant at 4% and 8% concentrations, with microcrystalline cellulose PH 102 (Pharma grade) and Ludipress as diluents.The core tablets were then compress coated with a slow-release component blend containing different grades of hydroxypropyl methylcellulose (HPMC) at various concentrations of HPMC E50, HPMC E15M, or HPMC E4M, as well as 4% Ethocel. Among all formulations, the F10 formulation containing HPMC E50 at 70% showed the best drug release, with 60% of the dose released slowly over 4 h, followed by an immediate burst of the remaining 40% at the 5th hour. The effect of different diluents on in vitro drug release kinetics and in vitro dissolution studies were performed for all formulations, and A1 formulation containing Cellactose-80 as a diluent showed the best results, with results matching the circadian variations in the disease condition.

Model-Based Evaluation of Drying Kinetics and Solvent Diffusion in Pharmaceutical Thin Film Coatings

Fluid-bed coating processes make it possible to manufacture pharmaceutical products with tuneable properties. The choice of polymer type and coating thickness provides control over the drug release characteristics, and multi-layer pellet coatings can combine several active ingredients or achieve tailored drug release profiles. However, the fluid-bed coating is a parametrically sensitive process due to the simultaneous occurrence of polymer solution spraying and solvent evaporation. Designing a robust fluid-bed coating process requires the knowledge of thin film drying kinetics, which in turn critically depends on an accurate description of concentration-dependent solvent diffusion in the polymer. This work presents a mathematical model of thin film drying as an enabling tool for fluid-bed process design. A custom-built benchtop drying cell able to record and evaluate the drying kinetics of a chosen polymeric excipient has been constructed, validated, and used for data collection. A semi-empirical mathematical model combining heat transfer, mass transfer, and film thickness evolution was formulated and used for estimating the solvent diffusion coefficient and solvent distribution in the polymer layer. The combined experimental and computational methodology was then used for analysing the drying kinetics of common polymeric excipients: poly(vinylpyrrolidone) and two grades of hydroxypropyl methylcellulose. The experimental setup together with the mathematical model represents a valuable tool for predictive modeling of pharmaceutical coating processes.

Optimization and Quest of HPMC loaded Stavudine Controlled Release Dosage Development by Central Composite Design utilizing Reduced Factorial Screening Technique

The current research focused on screening and finding the significant independent variables in stavudine loaded tablet, followed by optimizing the best formulation using central composite design. The objective of the study to develop stavudine loaded controlled release tablet utilizing reduced factorial design, followed by optimization technique as well as characterization of prepared tablets. Preliminary trial batches were prepared using different grades of hydroxypropyl methylcellulose. The resolution-IV reduced factorial design was selected to screen the significant independent variables in the dosage form design. A total number of eight runs were prepared and responses were recorded. The signified factors identified by half-normal and Pareto chart. The prepared tablets are evaluated for various physiochemical characterizations. Three dependent responses such as hardness, dissolution at 6 hour and 12 hours are considered in optimization process. Later on, drug-polymer interaction study was carried out. The principal of the study design based on finding the best formulation with prefixed set parameter values utilizing the concept of screening technique. It observed that HPMC K15M (57.18 %), HPMC K100 (66.32 %) and PVP K30 (7.97 %) as best composition in a formulation batch would fulfill the predetermined parameter with specific values.

Development and characterization of effervescent floating tablet of famotidine for treatment of peptic ulcer

Floating drug delivery systems (FDDS) are utilized to target drug discharge in the stomach or to the upper parts of intestine. Famotidine has been the most extensively used drug for the management of peptic ulcer for various decades. The current study concerns the development and evaluation of floating tablets of famotidine which, after oral administration, are planned to extend the gastric residence time, enhance drug bioavailability and aim the gastric ulcer. A FDDS was expanded using gas-forming agents, like sodium bicarbonate, citric acid and hydrocolloids, like hydroxypropyl methylcellulose (HPMC) and carbopol 934P. The prepared tablets were evaluated in terms of their pre-compression parameters, physical characteristics, buoyancy, buoyancy lag-time, in vitro release, and swelling index. The formulations were optimized for the different viscosity grades of HPMC, carbopol 934P and its concentrations and combinations. The consequences of the in vitro release studies demonstrated that the optimized formulation (F6) could sustain drug release (98%) for 24 h and remain buoyant for 24 hr. Optimized formulation (F6) showed no considerable change in physical appearance, drug content, total buoyancy time or in vitro dissolution study after storage at 40°C/75% RH for 3 months. Lastly the tablet formulations establish to be economical and may conquer the draw backs associated with the drug during its absorption.&#x0D; Keywords: Famotidine, Floating drug delivery system, Hydrocolloids, Gastric residence time.

Role of physicochemical properties of some grades of hydroxypropyl methylcellulose on in vitro mucoadhesion

Relationships between physicochemical properties of hydroxypropyl methylcellulose (HPMC) compacts and their in vitro mucoadhesive performances were investigated in this study. Some commercial grades of HPMC (K3, E3, E5, E50, K4M, E4M and K15M) were prepared into compacts, and their surface hydrophilicity and hydration behavior were characterized. The in vitro mucoadhesive performance was determined by the tensile strength between the compacts and different regions of mucosal membrane (buccal, sublingual, stomach, and intestine). Positive correlations were found between: (1) viscosity of HPMC compacts and contact angle in different simulated body fluids; (2) viscosity of HPMC compacts and in vitro mucoadhesive force; (3) contact angle and in vitro mucoadhesive force. The hydration increased with an increase in viscosity of HPMC compacts. The polar lipid content in mucosa was found to be an important factor affecting the mucoadhesion. Lower polar lipid amount in the mucosal membrane promoted the rate of mucoadhesive force with the increasing viscosity of HPMC. The mucoadhesive mechanism of various grades of HPMC compacts were studied using the thermodynamic analysis of Lifschitz-van der Waals (LW) interaction and Lewis acid-base (AB) interactions. The total free energy of adhesion (ΔGTOT) provided a prediction of an overall tendency of mucoadhesion, and deviated from the measured mucoadhesive force.

Formulation and evaulation of triazolam odts by direct compression forselection &amp; optimization of super disintegrates

Oral Disintegrating Tablets of Triazolam were formulated with an aim to improve the versatility, patient compliance, and accurate dosing. The formulations ere developed with an objective to use by the pediatric and geriatric patients. Triazolam Oral Disintegrating Tablets were prepared by direct compression method using cross povidone, croscarmellose sodium, sodium starch glycolate and combinations of CP+CCS, and CP + SSG as super disintegrates exhibited good pre-formulation and tableting properties of three super disintegrates, the formulation contained combination of CP + CCS showed better performance in terms of disintegration time when compared to other formulations. Order of the super disintegrates activity is as follows.&#x0D; (CP + CCS) &gt; (CP + SSG) &gt; CP &gt; CCS &gt;SSG&#x0D; The formulation F15 was found to be the best among all twenty Triazolam ODT formulations because it has exhibited faster disintegration time (17.66 sec) when compared to the other formulations and it showed 99.87±0.18% drug release at the end of 25 min. Triazolam Oral Disintegrating Films were prepared by solvent casting method using different grades of Hydroxypropyl Methyl Cellulose like HPMC – E15, HPMC – 5cps, HPMC – 50cps. Based on disintegration and dissolution results it was concluded that the formulation F15 contained CP 5% + CCS 5% was the best formulation among all otherformulations.

Loss-in-weight feeding, powder flow and electrostatic evaluation for direct compression hydroxypropyl methylcellulose (HPMC) to support continuous manufacturing

Minimizing variability in the feeding process is important for continuous manufacturing since materials are fed individually and can impact the final product. This study demonstrates the importance of measuring powder properties and highlights the need to characterize the feeding performance both offline with multiple refills and in the intended configuration for the continuous manufacturing equipment. The standard grade hydroxypropyl methylcellulose (HPMC) had material buildup on the loss-in-weight feeder barrel from triboelectric charging and resulted in more mass flow excursions and failed refills which were not observed with the direct compression grades. The location of the electrostatic buildup changed when the feeder was connected to a hopper instead of feeding offline into a collection bucket. Overall, the direct compression HPMC exhibited better flow which resulted in more accurate loss-in-weight feeding with less excursions from the target mass flow and all refills were completed in the first attempt. The improvements with the direct compression HPMC would be beneficial when running any continuous process (wet granulation, roller compaction, or direct compression) or other processes where loss-in-weight feeding is utilized, such as melt extrusion or twin screw granulation.

Hydroxypropyl Methylcellulose E15: A Hydrophilic Polymer for Fabrication of Orodispersible Film Using Syringe Extrusion 3D Printer.

Extrusion-based 3D printing technology is a relatively new technique that has a potential for fabricating pharmaceutical products in various dosage forms. It offers many advantages over conventional manufacturing methods, including more accurate drug dosing, which is especially important for the drugs that require exact tailoring (e.g., narrow therapeutic index drugs). In this work, we have successfully fabricated phenytoin-loaded orodispersible films (ODFs) through a syringe extrusion 3D printing technique. Two different grades of hydroxypropyl methylcellulose (HPMC E5 and HPMC E15) were used as the film-forming polymers, and glycerin and propylene glycol were used as plasticizers. The 3D-printed ODFs were physicochemically characterized and evaluated for their mechanical properties and in vitro disintegration time. Then, the optimum printed ODFs showing good mechanical properties and the fastest disintegration time were selected to evaluate their drug content and dissolution profiles. The results showed that phenytoin-loaded E15 ODFs demonstrated superior properties when compared to E5 films. It demonstrated a fast disintegration time in less than 5 s and rapidly dissolved and reached up to 80% of drug release within 10 min. In addition, it also exhibited drug content uniformity within United States Pharmacopeia (USP) acceptable range and exhibited good mechanical properties and flexibility with low puncture strength, low Young’s modulus and high elongation, which allows ease of handling and application. Furthermore, the HPMC E15 printing dispersions with suitable concentrations at 10% w/v exhibited a non-Newtonian (shear-thinning) pseudoplastic behavior along with good extrudability characteristics through the extrusion nozzle. Thus, HPMC E15 can be applied as a 3D printing polymer for a syringe extrusion 3D printer.

Development and Evaluation of Curcumin Floating Tablets

In the present study, curcumin an anti-inflammatory agent, was first complexed with the soluplus by hot melt extrusion machine to enhance the solubility of curcumin and was formulated into floating tablets by direct compression method. Tablets were formulated using various grades of Hydroxypropyl methylcellulose (HPMC) polymers and sodium bicarbonate as gas generating agent. Preformulation and micromeritic studies were performed. The floating tablets were evaluated for their physico-chemical properties, in-vitro release, in-vivo floating property, pharmacokinetic and stability studies. Formulations were found uniform with respect to thickness (5.11 to 5.27 mm) and hardness (4.4 to 4.8 kg/cm2). The friability (0.27 to 0.53 %), weight variation (1.28-1.89%) and Drug content (97.84 to 99.46 %). The order of swelling index of HPMC was found to be K100M > K15M > K4M. Sodium bicarbonate at the concentration of 16% w/w was found to be sufficient in attaining the buoyancy. The buoyancy lag time was found to be less than 1 minute for all the prepared tablets. The total floating time for different formulations was in the range of 12-24 hours. The optimized formulation F4, and F6 showed 98.85 and 98.10 % drug release at the end of 20 and 24 hrs respectively. The in-vivo floating study was carried out by X-ray imaging showed floating of the tablet in the stomach. The pharmacokinetic study showed, Cmax-260 ng/ml, Tmax-12 hrs, AUC -738.33 ng/hr/ml Kel as 0.061 and t1/2 was found to be 11.36 hrs. FT-IR, XRD and DSC studies revealed no chemical interaction between drug and polymers. During the stability period selected tablets were found to be stable with respect to floating behaviour and drug release characteristics.

Erodible coatings based on HPMC and cellulase for oral time-controlled release of drugs.

Oral drug delivery systems for time-controlled release, intended for chronotherapy or colon targeting, are often in the form of coated dosage forms provided with swellable/soluble hydrophilic polymer coatings. These are responsible for programmable lag phases prior to release, due to their progressive hydration in the biological fluids. When based on high-viscosity polymers and/or manufactured by press-coating, the performance of functional hydroxypropyl methylcellulose (HPMC) layers was not fully satisfactory. Particularly, it encompassed an initial phase of slow release because of outward diffusion of the drug through a persistent gel barrier surrounding the core. To promote erosion of such a barrier, the use of a cellulolytic product (Sternzym® C13030) was here explored. For this purpose, the mass loss behavior of tableted matrices based on various HPMC grades, containing increasing percentages of Sternzym® C13030, was preliminarily studied, highlighting a clear and concentration-dependent effect of the enzyme especially with high-viscosity polymers. Subsequently, Sternzym® C13030-containing systems, wherein the cellulolytic product was either incorporated into a high-viscosity HPMC coating or formed a separate underlying layer, were manufactured. Evaluated for release, such systems gave rise to more reproducible profiles, with shortened lag phases and reduced diffusional release, as compared to the reference formulation devoid of enzyme.

Robustness of Controlled Release Tablets Based on a Cross-linked Pregelatinized Potato Starch Matrix.

The aim of this study was to evaluate the potential of a cross-linked pregelatinized potato starch (PREGEFLO® PI10) as matrix former for controlled release tablets. Different types of tablets loaded with diprophylline, diltiazem HCl or theophylline were prepared by direct compression of binary drug/polymer blends. The drug content was varied from 20 to 50%. Two hydroxypropyl methylcellulose grades (HPMC K100LV and K100M) were studied as alternative matrix formers. Drug release was measured in a variety of release media using different types of experimental set-ups. This includes 0.1N HCl, phosphate buffer pH6.8 and water, optionally containing different amounts of NaCl, sucrose, ethanol or pancreatin, fasted state simulated gastric fluid, fed state simulated gastric fluid, fasted state simulated intestinal fluid, fed state simulated intestinal fluid as well as media simulating the conditions in the colon of healthy subjects and patients suffering from Crohn's disease. The USP apparatuses I/II/III were used under a range of operating conditions and optionally coupled with the simulation of additional mechanical stress. Importantly, the drug release kinetics was not substantially affected by the investigated environmental conditions from tablets based on the cross-linked pregelatinized potato starch, similar to HPMC tablets. However, in contrast to the latter, the starch-based tablets roughly kept their shape upon exposure to the release media (they "only" increased in size) during the observation period, and the water penetration into the systems was much less pronounced. Thus, the investigated cross-linked pregelatinized potato starch offers an interesting potential as matrix former in controlled release tablets.

Characterization of a novel hydroxypropyl methylcellulose (HPMC) direct compression grade excipient for pharmaceutical tablets.

Controlled release tablets are important dosage forms enabling a slower release of the drug and better pharmacokinetics for some drugs and hydrophilic matrix tablets utilizing hydroxypropyl methylcellulose (HPMC) are one of the most common types. One of the main challenges with using HPMC is its poor flow when implemented in a direct compression process or when utilized for continuous manufacturing for which novel grades of direct compression have been developed. In this work, three different direct compression (DC) grades of HPMC (K4M, K15M and K100M) were characterized and compared to their standard grade (CR) counterparts. These materials were compared in terms of density, particle size, morphology, surface area and powder flow using multiple techniques. Results showed that the materials were almost identical in terms of particle shape and although the DC grades had better flow, the particle size was slightly smaller with an unexpectedly higher surface area, which most likely resulted from the inclusion of co-processed silicon dioxide in the DC grades. The bulk, tapped and true densities were slightly higher for all of the DC grades. Of the eleven different parameters used to characterize the flow of the materials the DC grades showed better flow than their standard CR counterparts for nine of the parameters (Carr's Index, Erweka flow, FT4 Flow Rate Index, Mean Avalanche Time, Avalanche Scatter, Number of Avalanches, Shear Cell Uni-axial Compressive Strength and Shear Cell Flow Function Coefficient). Only the FT4 Basic Flowability Energy and Specific Energy showed the opposite trend which can be explained from the testing methodology. It is recommended to evaluate the DC grades of HPMC for processes where better flowing material would have an advantage, such as direct compression, continuous manufacturing, and roller compaction if the powder flow into the rolls is problematic.

Partial depolymerization of hydroxypropylmethyl cellulose for production of low molar mass polymer chains

Low molar mass (LMM) biopolymers are highly required to design functional nanomaterials, which mainly find application in biomedical fields. However, the synthesis of LMM polymer is a challenging task. In this work, we report a partial enzymatic depolymerization process which allows to produce a series of LMM hydroxypropylmethyl cellulose (HPMC) polymer, with a weight average molar mass (Mw) under and over 10,000 g mol−1 and low dispersity (Ɖ < 1.5). Variation of the starting HPMC grade, reaction time, and enzyme concentration were the key parameters to control the Mw and yield of the target molecules. This approach provides a versatile way of producing LMM HPMCs with varying degrees of substitution, and having a single reactive aldehyde function at one chain extremity. LMM HPMC can find for instance application as building blocks for the development of new functional molecular architectures.

Lysozyme Mucoadhesive Tablets Obtained by Freeze-Drying

Lysozyme is particularly attractive for the local treatment of oral pathologies related to microbiological infections. However, the requirement of a prolonged release is difficult to achieve because of saliva swallowing and of the protein denaturation which can occur during production and storage of a dosage form. This work demonstrates the feasibility to prepare lysozyme mucoadhesive tablets by freeze-drying. Tablets were prepared by using alginate (ALG) physically “cross-linked” with calcium ion and different grades of hydroxypropyl methylcellulose (HPMC) (i.e., E5, E50, or K100). The tablets were characterized in terms of swelling or erosion behavior, in vitro mucoadhesive properties, lysozyme activity (Micrococcus lysodeikticus), drug release and ability to inactivate Staphylococcus aureus. The formulations prepared with HPMC K100 were discarded because of the fast erosion. All other formulations allowed a sustained release over at least 6 h. Independently of composition, lysozyme activity (78,311 ± 1873 Units/mg) significantly decreased in the case of tablets containing 5% and 10% w/w of protein (55,000 Units/mg and 33,000 Units/mg, respectively). Conversely, no modifications occurred in the case of tablets containing 1% w/w lysozyme. The formulation prepared by ALG/HPMC E5 7/3 ratio was efficacious against S. aureus. After 3 months of storage at 5 ± 3°C, no significant decrease in lysozyme activity was observed.

Preparation and Evaluation of Rebamipide Film using Casting Technique for Local Action

Abstract&#x0D; The aim of this study was to prepare rebamipide ocular inserts in order to extend its release on the ocular surface for dry eye treatment. Solubility study was applied to the drug with or without l-arginine using different solvents. Solvent casting technique was used to prepare the inserts; l-arginine was used to solubilize the drug, hydroxypropyl methylcellulose grades (E5 and K15M) and poly ethylene glycol 200 were used as excipients. The inserts were evaluated for their physical and mechanical properties, moisture loss% and absorption %, surface pH, and in-vitro drug release. The use l-arginine exhibited an enhancement of rebamipide solubility in both deionized water and phosphate buffer (pH 7.4) by approximately 250 times and 3 times, respectively. The formulations showed uniform weight and thickness except for F1, and all showed uniform drug content. The absence of plasticizer in F1 caused haziness in its appearance and brittleness of the inserts. F3 which contain hydroxypropyl methylcellulose K15M showed good physical and mechanical properties thus was selected for in vitro release and was compared to the marketed brand Mucosta® suspension eye drop; F3 showed significant enhancement in extending the release of rebamipide compared to the reference marketed brand.&#x0D; Keywords: Rebamipide, L-arginine, Ocular insert, Solvent casting technique&#x0D; &#x0D; &#x0D; ???????&#x0D; ????? ?? ??? ??????? ?? ????? ?????????? ?????? ???? ???? ????? ??????????? ??? ??? ????? ????? ????? ?????. ??? ????? ??????? ?????? ????? ???????? ? ???? ????? ???????? ?????? ??????. ??????? ????? ??????? ? ???? ?????? ??????? ? ?????? ???????? ?????? ?????? ? ?? ??????? ??????????? ?????? ???? ???????? ?????? (K15M ? E5 ) ? ?????? ?????? ??????? ?????. ?? ????? ?????? ?????????? ? ?????????? ??????? ? ???? ?????? ??????? ??????? ????? ? ?????? ??????? ? ???? ???? ??????????? ???? ??????? ????? ????? ????? ?????? ?? ???????. ????? ??????? ?? ???????? ???? ??? ????? ??????? ???????????? ?? ?? ?? ????? ??????? ???????? ? ????? ???????? ?????? (?? ??????????? 7.4 ), ?????? ????? 250 ??? ? ???? ???? ??? ???????. ???????? ????? ??? ? ????? ??????? ???? ??? (F1 ) ? ?? ???????????? ????? ????? ?????? ????????. ??? ???? ???? ??(F1 ) ??? ??? ?????? ??????? ? ??????. ( F3) ???? ????? ??? ??????????? ?????? ???? ?????????? (M 15 K) ???? ???? ???????? ? ????????? ???? ? ??? ?? ??????? ?????? ??????? ?????? ?????? ?? ??????? ? ??????? ??????? ?????? ? ?? ????? ????? ????? ?????? ???? (????????) ? ?? ???? ?? ??????? F3 ???? ????? ???? ?? ????? ????? ???????????? ?????? ??????? ?????? ?????? ?????. &#x0D; ??????? ?????????: ??????????, ????????, ??????? ??????, ????? ??????? ? ????