Hydroxypropyl Methylcellulose E5 Research Articles

Fast disintegrating tablets of nisoldipine for intra-oral administration

Nisoldipine is a calcium channel blocker with low and variable oral bioavailability. This was attributed to slow dissolution and presystemic metabolism. Accordingly, the objective of this work was to enhance the dissolution rate of nisoldipine to formulate fast disintegrating tablets with rapid dissolution. Binary solid dispersions (SD) were prepared for the drug with hydroxypropyl methyl cellulose E5 (HPMC), polyvinylpyrrolidone (PVP), Pluronic F68 or polyethylene glycol 6000 (PEG 6000). SD formation increased the dissolution rate compared to pure drug with the corresponding physical mixtures failing to provide the same dissolution enhancement. This indicates that the SD enhanced dissolution is not due to the solubilizing effect of the polymer and can be due to physical change in the drug crystal which was confirmed by thermal analysis. SD with HPMC and PVP were selected for preparation of fast disintegrating tablets as they liberated most of the drug in the first 5 min. HPMC-based tablets disintegrated rapidly and released most of the drug in the first 2 min which correlated with the corresponding SD. In contrast, PVP-based tablets disintegrated slowly with gradual dissolution. This can be attributed to the binding effect of PVP. The study developed fast disintegrating tablet for intra-oral administration.

Design and evaluation of sustained release pellets of aceclofenac

AimThe aim of the present study was to prepare sustained release pellets of aceclofenac using pelletization technique. MethodsThe sustained release was ensured by coating the pellets with ethyl cellulose N50 and hydroxy propyl methyl cellulose E5. The influence of rate retarding polymer, ethyl cellulose in combination with film forming agent, HPMC in different weight ratios on drug release kinetics was studied. ResultsThe in vitro dissolution studies of aceclofenac from the sustained release pellets were carried out in pH 6.8 phosphate buffer using USP type I apparatus. Statistically significant differences were found among the drug release profile from different formulations. ConclusionThe kinetic study revealed that the release of drug from the optimized formulation was appeared to follow first order kinetics. The dissolution profile and in vitro release kinetics showed that aceclofenac pellets were promising for sustained delivery of the drug.

Oral buccoadhesive films of ondansetron: Development and evaluation

Introduction:Difficulty or inability in swallowing tablets/capsules during or after chemotherapy is common due to chemotherapy induced nausea and vomiting in patients. Buccoadhesive films of ondansetron hydrochloride were prepared for the prevention and treatment of chemotherapy-induced emesis. Films of varying polymeric composition were prepared in order to facilitate initial as well as prolonged drug release that could take care of acute as well as delayed emesis.Materials and Methods:Mucoadhesive films were prepared using polymers such as hydroxypropyl methylcellulose (HPMC) E5, HPMC K100, and Eudragit® NE 30 D. The effect of concentration of these polymers on physical properties and drug release were studied. All the films were prepared by solvent casting method. In another part of the study, the effect of drug concentration on physical and mucoadhesive properties of film were assessed, keeping the polymer concentration fixed.Results:Films containing HPMC showed good mucoadhesion. Increasing the concentration of Eudragit® NE 30 D in the films retarded drug release and increased residence time, however, reduced mucoadhesion. At a fixed polymer concentration and ratio, films prepared using an increased drug content showed an increased mucoadhesion.Conclusion:Films prepared using HPMC E5 (1000 mg), HPMC K100 (500 mg), and Eudragit® NE 30 D (750 mg) provided initial rapid followed by sustained drug release over a period of 6 h. Given the promising results, the study concluded that the developed buccal films have the potential to release ondansetron required for chemotherapy induced acute and delayed emesis.

Formulation Development and Characterization of Itraconazole Granules

Itraconazole is practically insoluble in water; large inter-individual and intra-individual variations of its oral bioavailability are reported. The main purpose of this study was to prepare and evaluate itraconazole granules for immediate release as drug delivery formulations. As a part of formulation optimization, different concentrations of hydroxy-propyl-methyl cellulose (HPMC) E5 were taken for the preparation of itraconazole granules, and were optimized with different characteristic like size, shape, surface roughness, density, moisture content, assay and dissolution. Formulation optimization includes a detailed study of itraconazole granules with different concentrations of polymer. The results of the study showed that 6% of HPMC E5 is sufficient as a binding agent and gave good shape and surface, low moisture content, 100% assay and 98.24% drug release within one hour. Based on these results, it can be concluded that 6% HPMC E5 is suitable for formulation of itraconazole granules.

Fabrication and in vitro evaluation of bidirectional release and stability studies of mucoadhesive donut-shaped captopril tablets

Objective: To obtain controlled release of captopril in the stomach, coated, mucoadhesive donut-shaped tablets were designed.Materials and methods: Donut-shaped tablet were made of different ratios of diluents to polymer or combination of polymers by direct compression method. Top and bottom portions of the tablet were coated with water-insoluble polymer followed by mucoadhesive coating. Time of water penetration, measurement of tensile strength, mucoadhesion studies (static ex vivo and ex vivo wash-off) were taken into account for characterization of respective films. In vitro study has been performed at different dissolution mediums. Optimized batches were also prepared by wet granulation. Stability studies of optimized batches have been performed.Results: The results of time of water penetration and tensile strength indicated positive response against water impermeation. Mucoadhesive studies showed that film thickness of 0.12 mm was good for retention of tablet at stomach. At pH 1.2, optimized batch of tablet made with hydroxypropyl methyl cellulose (HPMC) E15 as binder showed 80% w/w drug release within 4–5 h with maximum average release of 97.49% w/w. Similarly, maximum average releases of 96.36% w/w and 95.47% w/w were obtained with nearly same dissolution patterns using combination of HPMC E5 and HPMC E50 and sodium salt of carboxy methyl cellulose (NaCMC) 500–600 cPs instead of HPMC E15. The release profiles in the distilled water and pH 4.5 followed the above pattern except deviation at pH 6.8. Stability studies were not positive for all combinations.Conclusion: Coated, mucoadhesive donut-shaped tablet is good for controlled release of drug in the stomach.

Indomethacin sustained release pellets prepared by extrusion-spheronization

Gastrointestinal side effects may interrupt essential therapy with indomethacin, a non-steroidal anti-inflammatory drug. Formulation of this drug into sustained release multiparticulate form may reduce some of these side effects by avoiding contact of drug crystals with gastrointestinal mucosa at high concentrations, as may happen with immediate release dosage forms. Indomethacin (IM) sustained release pellets containing 5 or 10 % w/w of the drug were prepared using an extrusion-spheronization technique. Different concentrations of hydrophilic polymers, polyethylene glycol 4000 (PEG 4000), hydroxypropyl methylcellulose E5 LV premium (HPMC) and polyvinyl pyrrolidone (PVP K30), were mixed at different concentrations (5,10 and 20 %) with Avicel PH 101 to prepare the sustained release formulae. Moreover, a mixer torque rheometer was used to quantitatively determine the suitable moisture content in the pastes before the extrusion process. The resulting pellets were characterized for content, particle size, shape and dissolution profile. The studies on the effect of the polymers used on Avicel rheological properties revealed that the magnitude of torque for the system was decreasing as the polymer concentration increased. The in vitro release of IM from the prepared Avicel pellets was found to be dependent upon the type and concentration of the added polymer. The rank order of IM release in the presence of the investigated polymers was as follows: PEG > HPMC > PVP. Furthermore, the magnitude of IM release rate from the pellet formulations was found to be dependent on the magnitude of the peak torque of the pellet forming paste, which in turn depends on the type and concentration of the added polymer. Increasing IM loading from 5 to 10 % has led to an increase in dissolution rates. At least two of the prepared pellet formulations showed dissolution profiles similar to the commercial product Bonidon 75 SR capsules. In conclusion, the formulation of IM sustained release pellets successfully controlled the drug release which might be beneficial in lowering the risk of side effects and improving patient convenience as an advantage of the pellets as a drug delivery system.

Gefitinib–cyclodextrin inclusion complexes: physico-chemical characterization and dissolution studies

Background: Gefitinib, an anticancer drug, has an extremely low aqueous solubility, and its oral absorption is limited by its dissolution rate. The solubility and dissolution of gefitinib can be improved by complexation with cyclodextrins (CDs). Methods: Phase solubility studies of gefitinib with hydroxypropyl βCD (HPβCD) and randomly methylated βCD (RMβCD) in n various aqueous systems was conducted to characterize the complexes in the liquid state. The inclusion complexes in the solid state were prepared by freeze-drying method and characterized by X-ray diffractometry (X-RD) and differential scanning calorimetry (DSC). Results: Gefitinib formed stable complexes with HPβCD and RMβCD in distilled water as indicated by the association rate constants (Ks) of 458.9 and 1096.2 M−1 for HPβCD and RMβCD, respectively. The complexation of gefitinib with CDs in pH 4.5 acetate buffer indicated an AN type of phase-solubility diagrams, whereas gefitinib and HPβCD in distilled water in the presence of polymers such as polyvinyl pyrrolidone K-30 (PVP) or hydroxypropyl methylcellulose E3 (HPMC) resulted in AP-type phase-solubility diagrams. The solid-state amorphous complexes (as described by DSC and X-RD) showed substantial increases in the solubility and dissolution rate of gefitinib with both CDs. Further increases in the solubility and dissolution rate of the gefitinib-HPβCD freeze-dried complex were obtained by physically mixing the complex with PVP and HPMC. Conclusion: Gefitinib formed stable inclusion complexes with HPβCD and RMβCD, and the solubility and dissolution rate of the drug was significantly increased.

A Novel Intravaginal Delivery System for Itraconazole: In Vitro and In Vivo Evaluation

The purpose of the present study was to formulate and systematically evaluate in vitro, ex vivo and in vivo performances of itraconazole containing bioadhesive vaginal film. We introduce here a novel intravaginal delivery system for itraconazole based on solid dispersion of itraconazole and hydroxypropyl methylcellulose E15 that improve drug solubility and produce bioadhesive system in presence of other ingredients. Solid dispersions of itraconazole were prepared with hydroxypropyl methylcellulose by a spray drying method and characterized by X-ray diffraction and differential scanning calorimetry. The film was prepared using a solvent evaporation technique. In the in vitro antimicrobial study, it was found that solid dispersion containing formulation improves antimicrobial action of itraconazole. From the ex vivo retention study, it was found that the bioadhesive polymers hold the film upto 7 hours on the vaginal mucosa. In vivo antifungal activity tested against Candida albicans vaginitis in female rats, was found to significantly improve the therapeutic benefit of the drug. At 6 days post-dose, the c.f.u. of Candida albicans was more than 10(3) fold decreased in film treated groups without affecting the morphology of vaginal mucosa. These studies suggested that bioadhesive vaginal film is a novel approach for delivery of itraconazole as topical drug delivery system for treating vaginal candidiasis.

Chronomodulated drug delivery system of salbutamol sulphate for the treatment of nocturnal asthma

A time dependent pulsed release system consisting of an effervescent core surrounded by consecutive layers of swelling and rupturable polymers was prepared and evaluated. The cores containing salbutamol sulphate as bioactive agent were prepared by direct compression method using different ratios of microcrystalline cellulose and effervescent agent and then coated sequentially with an inner swelling layer containing a hydrocolloid, hydroxypropylmethylcellulose E5 and an outer rupturable layer having Eudragit RL/RS (1:1). The effects of various processing and formulative parameters on the performance of system were studied. The rupture and dissolution tests were studied using the USP paddle method at 50 rpm in 0.1 N HCl and phosphate buffer pH 6.8. The lag time of the drug release decreased by increasing the inner swelling layer and increased by increasing the rupturing layer level. All the results obtained in the present study suggest that osmotic pumping effect was involved which eventually lead to the drug release.

Preparation of Theophylline-Hydroxypropylmethylcellulose Matrices Using Supercritical Antisolvent Precipitation: A Preliminary Study

ABSTRACTSeveral controlled release systems of drugs have been elaborated using a supercritical fluid process. Indeed, recent techniques using a supercritical fluid as a solvent or as an antisolvent are considered to be useful alternatives to produce fine powders. In this preliminary study, the effect of Supercritical Anti Solvent process (SAS) on the release of theophylline from matrices manufactured with hydroxypropylmethylcellulose (HPMC) was investigated. Two grades of HPMC (HPMC E5 and K100) as carriers were considered in order to prepare a sustained delivery system for theophylline which was used as a model drug. The characterization of the drug before and after SAS treatment, and the coprecipitates with carriers, was performed by X-ray Diffraction (XRD) and Differential Scanning Calorimetry (DSC). The dissolution rate of theophylline, theophylline-coprecipitates, and matricial tablets prepared with coprecipitates were determined. The physical characterizations revealed a substantial correspondence of the drug solid state before and after supercritical fluid treatment while drug-polymer interactions in the SAS-coprecipitates were attested. The dissolution studies of the matrices prepared compressing the coprecipitated systems showed that the matrices based on HPMC K100 were able to promote a sustained release of the drug. Further, this advantageous dissolution performance was found to be substantially independent of the pH of the medium. The comparison with the matrices prepared with untreated substances demonstrated that matrices obtained with SAS technique can provide a slower theophylline release rate. A new mathematical model describing the in vitro dissolution kinetics was proposed and successfully tested on these systems.

In situ gelling, bioadhesive nasal inserts for extended drug delivery: In vitro characterization of a new nasal dosage form

The purpose of this study was the preparation and characterization of sponge-like, in situ gelling inserts based on bioadhesive polymers. Hydrophilic polymers (carrageenan, Carbopol, chitosan, hydroxypropyl methylcellulose (HPMC) K15M and E5, sodium alginate, sodium carboxy methylcellulose (NaCMC), polyvinyl pyrrolidone (PVP) 90, xanthan gum) were dissolved with/without the model drug oxymetazoline HCl in demineralized water and lyophilized into small inserts. The drug release, water uptake, mechanical properties, X-ray diffraction and bioadhesion potential of the nasal inserts were investigated. A sponge-like structure of nasal inserts was formed with amorphous, but not with crystalline polymers during the freeze-drying process. The insert hardness increased with the glass transition temperature of the polymer (PVP25 < PVP30 < PVP90). The bioadhesion potential was governed by the polymer ability to interact with mucin/agar (highest for carrageenan, Carbopol, xanthan gum and NaCMC). Inserts prepared from low molecular weight polymers resulted in polymer dissolution and fast drug release (HPMC E5, Na-alginate, PVP90). The drug release from inserts prepared from high molecular weight polymers (carrageenan, Carbopol, chitosan, HPMC K15M, NaCMC, xanthan gum) was a complex interplay of osmotic forces, water uptake and electrostatic interactions between drug and polymer. The drug release decreased with higher polymer content and increased drug loading of the insert. Bioadhesive nasal inserts have a high potential as new nasal dosage form for extended drug delivery.

Study of Drug Release from Pellets Coated with Surelease Containing Hydroxypropylmethylcellulose

The release of metoclopramide hydrochloride (a very water soluble cationic drug) and diclofenac sodium (a sparingly soluble anionic drug) from pellets coated with Surelease containing hydroxypropylmethylcellulose (HPMC) at different coating loads was investigated. The release rates of either drug at each coating composition decreased as the coating load increased. Inclusion of HPMC E15 increased the release rates of both drugs compared to pellets coated only with Surelease. This was thought to be due to the leakage of the soluble part of the film (HPMC E15) during dissolution, which left pores for drug release. The Surelease:HPMC E15 ratio had a major role in the release rates of drugs. Addition of HPMC E15 into Surelease did not change the release mechanism for metoclopramide hydrochloride (the mean value of n ≈ 0.57) from that of Surelease alone, and diffusion remained the main mechanism controlling the release. However, the release exponent (≈1.28) increased for diclofenac sodium on addition of HPMC E15, indicating a dissolutioncontrolled mechanism. Despite its lower water solubility, diclofenac sodium was released slightly faster than metoclopramide hydrochloride from pellets coated with Surelease containing HPMC E15 at equivalent coating loads.

Tableting of controlled release multiparticulates, the effect of millisphere size and protective overcoating

Controlled release enalapril millispheres of different diameters were prepared and tableted with excipients in a 1:1 ratio on a Carver press. Drug release rate profiles showed that the microporous coating on the millispheres was severely damaged during the compression process. Overcoating of the microporous coating with hydroxypropyl methylcellulose E5 (HPMC E5) protects the microporous coating during compression by absorbing and dissipating the compressional forces. This protection becomes more pronounced as the size of the millispheres is reduced. A novel investigation of individual millisphere strength was conducted to identify the most favorable coating and size combination which would preserve the controlled release properties of the millispheres.

Calorimetric Studies of Dissolution of Hydroxypropyl Methylcellulose E5 (HPMC E5) in Water

The interaction of water with polymers is important because it directly or indirectly affects various properties such as rheological and transport properties. In this study, the hydration/dissolution of a hydrophilic polymer was investigated by calorimetric techniques. Hydroxypropyl methylcellulose E5 (Methocel, HPMC E5) was used as the model polymer. A water-insoluble, hydrophobic polymer, ethyl cellulose E4 (Ethocel, EC E4), was selected for comparison. The number of moles of non-freezing and freezing water were determined by differential scanning calorimetry. Moles of non-freezing water per polymer repeat unit were 6.2 ± 1.3 and 1.6 ± 0.3 for HPMC E5 and EC E4, respectively. The hydration/dissolution of HPMC E5 was exothermic, with a total heat of dissolution of –24.1 ± 1.1 cal/g (n = 4). The heat of hydration of water-insoluble EC E4 was –2.6 cal/g (n = 2). The specific heat capacity value of HPMC E5 increased due to the addition of water. The heat of solution and an increase in specific heat capacity values were associated mainly with the addition of tightly bound water to the polymer. The dissolution of HPMC E5 in water is believed to have endothermic and exothermic components. In summary, the study provided insight into the dissolution of a representative hydrophilic polymer in water. The heat of solution and the specific heat capacity values were mainly dependent on the addition of tightly bound water.