Avicel PH Research Articles

Sustained release enteric coated tablets of pantoprazole: Formulation, in vitro and in vivo evaluation

In this study, an attempt was made to deliver pantoprazole in a sustained manner using delayed release tablets. The tablets were prepared by the wet granulation method using HPMC, cassava starch and polyvinyl pyrrolidine as polymers, Avicel PH 102 (MCC) as filler and potato starch as binder. The prepared tablets were evaluated for hardness, mass variation, friability and drug content uniformity, and the results were found to comply with official standards. The prepared tablets were coated using an enteric coating polymer such as cellulose acetate phthalate, Eudragit L100 and drug coat L100 by the dip coating method. The in vitro release was studied using pH 1.2 acidic buffer and pH 6.8 phosphate buffer and the study revealed that the prepared tablets were able to sustain drug release into the intestine. The anti-ulcer activity was evaluated by a water immersion stress induced ulcer model. The enteric coated pantoprazole tablets significantly reduced ulcer formation.

Development and Evaluation of Chronotherapeutic Drug Delivery System for the Management of Nocturnal Asthma

Purpose: To develop an oral capsule-based chronomodulated drug delivery system of salbutamol sulphate for the treatment of nocturnal asthma.Methods: The basic design of the proposed dosage form entails an insoluble cross-linked capsule body filled with drug-loaded pellets sealed with hydrocolloid plug and a soluble capsule cap. Various hydrocolloid polymers, namely, hydroxypropyl methylcellulose, (HPMC), hydroxypropyl cellulose (HPC), sodium alginate, polyethylene oxide (PEO) and guar gum. were used to optimize the plug material in the delivery in order to modulate lag period To avoid gastric transit time variability, the entire system was coated with Eudragit S100/Eudragit L100 dispersion (4:1), an enteric polymer system that dissolves at pH 6.8.Results: Time-specific pulsatile release with 4 h lag period was achieved with crosslinked insoluble gelatin capsule shells containing pellets prepared from Avicel PH 101/lactose (80: 10) and 3 % Acidisol as disintegrant. In vitro data indicate that the developed pulsatile system released almost 98 % of the drug shoertly after the predetermined lag time of 4 h.Conclusion: The developed system is capable of releasing the drug after a 4-h lag period. However, in vivo studies need to be carried out to ascertain the effectiveness of the formulation. Keywords: Time controlled, pH-controlled, Lag time, pulsed release, Hydrocolloid plug, Nocturnalasthma

Use of First Derivative of Displacement vs. Force Profiles to Determine Deformation Behavior of Compressed Powders

Displacement (D) vs. force (F) profiles obtained during compaction of powders have been reported by several researchers. These profiles are usually used to obtain mechanical energies associated with the compaction of powders. In this work, we obtained displacement-force data associated with the compression of six powders; Avicel PH101, Avicel PH301, pregelatinized corn starch, anhydrous lactose, dicalcium phosphate, and mannitol. The first three powders are known to deform predominantly by plastic behavior while the later ones are known to deform predominantly by brittle fracture. Displacement-force data was utilized to perform in-die Heckel analysis and to calculate the first derivative (dD/dF) of displacement-force plots. First derivative results were then plotted against mean force (F') at each point and against 1/F' at compression forces between 1 and 20 kN. Results of the in-die Heckle analysis are in very good agreement with the known deformation behavior of the compressed materials. First derivative plots show that materials that deform predominantly by plastic behavior have first derivative values (0.0006-0.0016 mm/ N) larger than those of brittle materials (0.0004 mm/N). Moreover, when dD/dF is plotted against 1/F' for each powder, a linear correlation can be obtained (R2=>0.98). The slopes of the dD/dF vs. 1/F' plots for plastically deforming materials are relatively larger than those for materials that deform by brittle behavior. It is concluded that first derivative plots of displacement-force profiles can be used to determine deformation behavior of powders.

A model for estimating the medium properties of Avicel to ethanol conversion

Simultaneous saccharification and fermentation received an increasing level of attention over recent decades, with the primary focus on the development of improved enzyme and organism performance. Little literature is available on the effects of the various fermentation components on the apparent dynamic viscosity of the fermentation broth for use in reactor design and analysis. This work investigates density and settling properties of Avicel PH-101 particles and the effects of base medium composition, yeast concentration and cellulose particles on the apparent dynamic viscosity of the fermentation mixture. Dynamic viscosity measurements were obtained using a rotational viscometer equipped with a DG 26.7 double gap concentric cylinder measuring system. Results indicated that Avicel particles experience a greater drag force compared to similar sized spherical particles and have a measured density of 1,605.7kgm(-3). The Ostwäld-de Waele formulation was used to describe the dynamic viscosity of the particles due to it shear-thinning nature. Correlation between the predicted particle effects and experimental results deviated with a root mean square error of 8.46%.

Bioavailability Studies of Ketorolac Tromethamine Fast Dissolving Tablets Prepared By Direct Compression Method

This study was concerned with the investigation of acute pharmacological responses (pharmacodynamics) including analgesic and anti-inflammatory effects of ketorolac tromethamine fast dissolving tablets prepared by direct compression method using 3% croscarmellose sodium as a superdisintegrant by applying tail flick test and carragenan induced rat paw edema test respectively. Also, the work aimed to develop a sensitive LC-MS/MS method for simultaneous determination of ketorolac tromethamine in human plasma samples released from fast dissolving tablets. Also, to estimate whether the prepared tablet dosage form increases the bioavailability of ketorolac tromethamine in the body compared to marketed conventional tablet. From this study, it could be inferred that ketorolac tromethamine fast dissolving tablets (G5) containing (3% corscarmellose sodium as a superdisintegrant, 30% Avicel pH102, 5% aspartame, 1% talc, 1% magnesium stearate, and mannitol Q.S.) and prepared by direct compression method could be considered as a promising formula to enhance bioavilability of the drug. Keyword: Ketorolac tromethamine fast dissolving tablet , Tail flick, Rat paw edema and bioavialbility

Comparative release profile of sustained release matrix tablets of verapamil HCl

Introduction:Verapamil hydrochloride (VH) is a calcium channel blocking agent used in the treatment of hypertension, cardiac arrhythmia and angina pectoris. The short half-life and high frequency of administration of VH makes it a suitable candidate for designing sustained drug delivery system. The aim of the present investigation was to develop a sustained release matrix tablet of verapamil hydrochloride (VH) using ethyl cellulose, methyl cellulose, Eudragit RS 100, hydroxypropyl methylcellulose and carboxymethyl cellulose and to evaluate the drug release kinetics.Materials and Methods:In order to achieve the required sustained release profile, the tablets were prepared by a wet granulation method using avicel PH 101 and magnesium stearate as binder and lubricant, respectively.Results:The formulated tablets were characterized for pre-compression and post-compression parameters and they were in the acceptable limits. The drug release data obtained after an in vitro dissolution study was fitted to various release kinetic models in order to evaluate the release mechanism and kinetics. The criterion for selecting the best fit model was linearity (coefficient of correlation). Drug release mechanism was found to follow a complex mixture of diffusion, swelling and erosion. Furthermore, to minimize the initial burst drug release, batches were coated by using Eudragit RS100 polymer. After coating the tablets, a better release profile of the formulated tablets was expected and the release rate of the drug was compared with the marketed SR tablet of VH.Conclusion:The dosage form holds the potential to control the release rate of drug and extend the duration of action of a drug.

Pharmacokinetic-Pharmacodynamic Model of Newly Developed Dexibuprofen Sustained Release Formulations

Pharmacokinetic-pharmacodynamic (PK-PD) modeling has emerged as a major tool in clinical pharmacology to optimize drug use by designing rational dosage forms and dosage regimes. Quantitative representation of the dose-concentration-response relationship should provide information for the prediction of the level of response to a certain level of drug dose. This paper describes the experimental details of the preformulation study, tablet manufacture, optimization, and bioanalytical methods for the estimation of dexibuprofen in human plasma. The hydrophilic matrix was prepared with xanthen gum with additives Avicel PH 102. The effect of the concentration of the polymer and different filler, on the in vitro drug release, was studied. Various pharmacokinetic parameters including AUC0–t, AUC0–∞, C max, T max, T 1/2, and elimination rate constant (K el) were determined from the plasma concentration of both formulations of test (dexibuprofen 300 mg) and reference (dexibuprofen 300 mg tablets). The merits of PK-PD in the development of dosage forms and how PK-PD model development necessitates the development of new drugs and bio analytical method development and validation are discussed. The objectives of the present study, namely, to develop and validate the methods to estimate the selected drugs in the biological fluids by HPLC, the development of in vitro dissolution methods, and PK-PD model development have been described.

Enhancement of Dissolution of Telmisartan by Surface Solid Dispersion Technique

Telmisartan is an Angiotensin Receptor Blocker (ARB) used for the treatment of hypertension. It belongs to BCS class-II i.e. low solubility and high permeability and exhibits variable bioavailability. The objective of the present study was to prepare surface solid dispersions of telmisartan to improve its aqueous solubility and dissolution rate. Water insoluble carriers like Avicel pH 101, Crospovidone, Sodium starch glycolate, Cab-o-sil, Pregelatinised starch and Potato starch were used to form surface solid dispersion (SSD) of Telmisartan by solvent evaporation method. The surface solid dispersion prepared with Cab-o-sil in the drug : carrier ratio of 1:10 showed highest dissolution rate as compared to pure drug and physical mixture. The SSD on Cab-o-sil was characterized by Powder X-ray diffractometry, Differential scanning calorimetry, Fourier transform infrared spectroscopy and Scanning electron microscopy. DSC studies revealed that there was no chemical interaction between drug and the carrier and XRD studies demonstrated that there was a significant decrease in crystallinity of pure drug .The optimized surface solid dispersion was compressed into tablets and evaluated for Weight variation, Hardness, friability, Drug content, Disintegration time and Dissolution rate. These tablets exhibited higher rates of dissolution and dissolution efficiency as compared to marketed tablets.

Cellulase immobilized by sol–gel entrapment for efficient hydrolysis of cellulose

Cellulase from Trichoderma reesei (Celluclast 1.5L, Novozyme) was immobilized by sol-gel encapsulation, using binary or ternary mixtures of tetramethoxysilane (TMOS) with alkyl- or aryl-substituted trimethoxysilanes as precursors. Optimization of immobilization conditions resulted in 92% recovery of total enzymatic activity in the best immobilized preparate. The immobilized cellulase exhibiting the highest activity, obtained from tetramethoxysilane and methyltrimethoxysilane precursors at 3:1 molar ratio, was investigated in the hydrolysis reaction of microcrystalline cellulose (Avicel PH101). Although the optimal values did not change significantly, both temperature and pH stabilities of the sol-gel entrapped cellulase improved compared to the native enzyme. Immobilization also conferred superior resistance against the inactivation effect of glucose. Reuse of the sol-gel entrapped cellulase showed 40% retention of the initial activity after five batch hydrolysis cycles, demonstrating the potential of this biocatalyst for large-scale application.

<em>In-vitro</em> Release Study of Carvedilol Phosphate Matrix Tablets Prepared with Hydroxypropyl Methylcellulose

Purpose: To evaluate the effect of two molecular weight grades of hydroxypropyl methylcellulose on the release characteristics of carvedilol phosphate matrix tablets. Methods: Matrix tablets containing carvedilol phosphate were prepared from 27 formulations in three batch series coded A, B and C, each containing 9 formulations. Each batch incorporated different ratios of two molecular weight grades of hydroxypropyl methylcellulose (Methocel ® K4M CR and K15M CR) used as release retarding agents. Microcrystalline cellulose (Avicel PH 101), starch (Sta-Rx 1500) and lactose monohydrate were used as diluents in the formulations while the effect of sodium lauryl sulphate (wetting agent) was studied for some of the formulations. The tablets were characterized for carvedilol phosphate release in both simulated gastric and intestinal fluids. The data were subjected to different models in order to determine their release kinetics and mechanisms. Results: All the batches released more than 50 % of their carvedilol content in 12 h when Methocel ® K4M CR and K15M CR constituted 18 % and 15 % of the matrix, respectively. Avicel ® PH 101 decreased while Starch 1500 and lactose monohydrate increased drug release. Drug release mechanism was predominantly diffusion. Conclusion: By using varying combinations of two molecular weight grades of hydroxypropyl methylcellulose as the matrix, controlled or sustained release carvedilol tablets of varying release characteristics can be prepared.

Influence of Disintegrant on Properties of Fast Disintegrating Tablet Containing Xylitol

Disintegrants had influence on disintegration time and dissolution for fast disintegrating tablet (FDTs). Therefore, the purpose of this study was to evaluate the effect of disintegrant type on the characteristics of FDTs. In this research, the tablets were fabricated by direct compression with the compression force of 1.5 tons and using the different disintegrants components (chitin, chitosan, xylitol, microcrystalline celluloses, white bentonite and magnabite F). The physical properties of these tablets were determined. The xylitol tablets were rapidly disintegrated within 7+1 s, whereas that of the others was longer than 30 mins. The tablets containing the mixture of xylitol and other materials were subsequently fabricated since the hardness of the xylitol tablet was very poor. The disintegration time and wetting time of tablets containing 9:1 xylitol:Avicel PH101 was shorter than that of the others. The contact angle of tablets containing xylitol and Avicel PH101 at the ratio of 9:1 was lowest and surface free energy (SFE) of them was highest compared with the other formula. Moreover, scanning electron microscope (SEM) displayed that xylitol and tablets containing 9:1 xylitol:Avicel PH101 had no disordered arrangement, therefore it could promote the disintegrating property effectiently.

THE USE OF KETOPROFEN NIOSOMES FOR FORMULATION OF SUSTAINED RELEASE TABLET DOSAGE FORM

The objective of this study was to formulate sustained release tablet dosage form (100 mg) using Ketoprofen Niosomes. Ketoprofen Niosomes were prepared by lipid hydration method and then dried and compressed into sustained release tablets (100 mg). The tablet excipients employed include: Avicel PH 101, Avicel PH 102, and Mannitol as diluents, Cab-O-Sil (colloidal silica) as a glidant, Starch as a disintegrant and Magnesium Stearate as lubricating agent. The tablets were tested for weight variation, hardness, friability, thickness, disintegration, drug content and release ratio. Finally the release kinetics of Ketoprofen tablets were calculated.

Effect of Excipients on Oxcarbazepine Release from Modified Release Matrix Tablets

The present investigation was undertaken with an objective of formulating modified release (MR) matrix tablets of Oxcarbazepine (OXC) an anti-epileptic drug, based on cellulose ether polymers like Hydroxy Propyl Methyl Cellulose (HPMC K4M and LVCR 100) and Hydroxy Propyl Cellulose (HPC JF) as drug release retardants to overcome poor patient compliance and exposure to high doses associated with currently marketed immediate release (IR) dosage forms. The tablets were prepared by direct compression process and evaluated for various physico- chemical/mechanical parameters. Among three polymers used, HPMC LVCR 100 is selected as release retardant based on the viscosity and gel formation during dissolution. The effect of different fillers like Avicel PH 101, Avicel PH 105, Pre gelatinized starch (PGS), maize starch with spray dried lactose (FLOWLAC) and Di-calcium phosphate (DCP) on OXC release was also studied and the OXC percent release at the end of 12h is in the order of DCP>FLOWLAC>Avicel PH 101>Avicel PH 105>PGS. Based on the dissolution data obtained with different fillers and keeping in view of the results from the pre compression studies, and gel layer retaining with the matrix tablets, Avicel PH 105 was selected as carrier to carry out further formulation development. Since, OXC is poorly water soluble drug, solubilizing agents like surfactants, cyclodextrins and polyethylene glycols were included in the formulations and their effect on OXC release was studied in order to achieve therapeutic effective levels. Formulations containing 20% (w/w) of Hydroxy Propyl-β-Cyclodextrin gave superior OXC release of 85.50 ± 1.62% at the end of 12hours and fulfils the regulatory requirement. The dissolution data was also evaluated for drug release kinetics and mechanisms.

Use of the liquisolid compact technique for improvement of the dissolution rate of valsartan

The aim of this study was to improve the dissolution rate of the poorly soluble drug valsartan by delivering the drug as a liquisolid compact. Liquisolid compacts were prepared using propylene glycol as solvent, Avicel PH102 as carrier, and Aerosil 200 as the coating material. The crystallinity of the newly formulated drug and the interaction between excipients was examined by X-ray powder diffraction and Fourier-transform infrared spectroscopy, respectively. The dissolution studies for the liquisolid formulation and the marketed product were carried out at different pH values. The results showed no change in the crystallinity of the drug and no interaction between excipients. The dissolution efficiency of valsartan at 15min was increased from 4.02% for plain drug and 13.58% for marketed product to 29.47% for the liquisolid formulation. The increase in the dissolution rate was also found to be significant compared to the marketed product at lower pH values, simulating the gastric environment where valsartan is largely absorbed. The liquisolid technique appears to be a promising approach for improving the dissolution of poorly soluble drugs like valsartan.

Cholorpheniramine tannate complexes: Physicochemical, chemometric, and taste masking evaluation

The focus of present investigation was to evaluate the tannic acid (TA) complexes of cholorpheniramine maleate (CPM) and characterize it by a variety of physicochemical, dissolution, and electronic tongue methods. The complexes were prepared in various molar ratios by solvent evaporation method. They were characterized by spectroscopic, thermal, powder X-ray, electronic tongue, solubility and dissolution methods. FTIR (infrared red) spectra showed complex formation between the TA and CPM. Complex formation has significantly lowered the drug solubility and sustained its release for more than 24 h in phosphate buffer pH 6.8. On the contrary, the release was much faster in the presence of Avicel PH 113 in the same molar ratio complex. The complex formulation has suppressed the bitter taste of CPM as indicated by Euclidean distance in electronic tongue evaluation. NIR-CI (near infrared chemical imaging) showed lower skew value that indicated the homogenous distribution of formulation components. The chemometric models were also developed using the NIR data. The model based on second derivative data was better in predicting the TA and CPM loading as indicated by higher values of R, R(2) and lower values of root mean square error and standard errors. Furthermore, it has a better accuracy and less biased in comparison to other models. In conclusion, the CPM tannate has a sustained release behavior and excipients play a major role in modifying its release. Additionally, the complexes with varying molar ratio of tannate to CPM have differential taste masking abilities than that of the pure drug.

Investigation on in vitro dissolution rate enhancement of indomethacin by using a novel carrier sucrose fatty acid ester

Background and the purpose of the studyThe purpose of the present investigation was to characterize and evaluate solid dispersions (SD) of indomethacin by using a novel carrier sucrose fatty acid ester (SFE 1815) to increase its in vitro drug release and further formulating as a tablet.MethodsIndomethacin loaded SD were prepared by solvent evaporation and melt granulation technique using SFE 1815 as carrier in 1:0.25, 1:0.5 1:0.75 and 1:1 ratios of drug and carrier. Prepared SD and tablets were subjected to in vitro dissolution studies in 900 mL of pH 7.2 phosphate buffer using apparatus I at 100 rpm. The promising SD were further formulated as tablets using suitable diluent (DCL 21, Avicel PH 102 and pregelatinised starch) to attain the drug release similar to that of SD.. The obtained dissolution data was subjected to kinetic study by fitting the data into various model independent models like zero order, first order, Higuchi, Hixon-Crowell and Peppas equations. Drug and excipient compatibility studies were confirmed by fourier transform infrared spectroscopy, X-ray diffraction, differential scanning calorimetry and scanning electron microscopy.ResultsThe in vitro dissolution data exhibited superior release from formulation S6 with 1:0.5 drug and carrier ratio using solvent evaporation technique than other SDs prepared at different ratio using solvent evaporation and melt granulation technique. The in vitro drug release was also superior to that of the physical mixtures prepared at same ratio and also superior to SD prepared using common carriers like polyvinyl pyrollidone and PEG 4000 by solvent evaporation technique. Tablets (T8) prepared with DCL21 as diluent exhibited superior release than the other tablets. The tablet formulation (T8) followed first order release with Non-Fickian release.ConclusionSFE 1815 a novel third generation carrier can be used for the preparation of SD for the enhancement of in vitro drug release of indomethacin an insoluble drug belonging to BCS class II.

COMPATIBILITY STUDIES OF ACETAZOLAMIDE WITH EXCIPIENTS BY USING HIGHPERFORMANCE LIQUID CHROMATOGRAPHY (HPLC) TECHNIQUE

Compatibility studies are essential for preformulation studies of formulation development. Acetazolamideis a carbonic anhydrase inhibitor used in the treatment and management of cardiac oedema, glaucomaand other conditions. The objective of this study was to evaluate the physical and chemical stability ofacetazolamide, when mixed with excipients as binary mixture. These samples were stored and evaluatedfor related substances at 400/75 % RH for 28 days and 550 for 14 days and the samples were analyzedusing HPLC. The results demonstrated the suitability of acetazolamide with Avicel PH 101, MethocelK4M premium CR hydroxy propyl methyl cellulose, Methocel E10M premium CR hydroxy propyl methylcellulose, talc, sodium lauryl sulphate and size 00 white/white hard gelatin capsule.

Mixed 3-mono-O-alkyl cellulose: Synthesis, structure characterization and thermal properties

The 3-mono-O-alkyl cellulose samples bearing two different ether moieties, namely methyl/ethyl, methyl/n-propyl, and ethyl/n-propyl were synthesized applying protecting group technique. The NMR spectra of the peracetylated products revealed the regioselectivity of the alkylation as well as the degree of substitution of both alkyl moieties. The number average degree of polymerization (DPn) monitored by size exclusion chromatography decreases from DPn 117 (Avicel PH-101, starting material) to DPn 34 (sample 4f) due to the multi-step synthesis. It could be demonstrated that the lower critical solution temperature (LCST) is influenced by the degree of substitution of both alkyl groups. For example, LCST values between 33 and 58°C were measured for aqueous solutions of 3-mono-O-ethyl/n-propyl cellulose. On the contrary, the thermal behavior of a physical mixture of 3-mono-O-ethyl- and 3-mono-O-n-propyl cellulose, e.g., was controlled by the derivative with the lowest LCST.

Characterization, optimisation and process robustness of a co-processed mannitol for the development of orally disintegrating tablets

This is a study to fully assess a commercially available co-processed mannitol for its usefulness as an off-the-shelf excipient for developing orally disintegrating tablets (ODTs) by direct compression on a pilot scale (up to 4 kg). This work encompassed material characterization, formulation optimisation and process robustness. Overall, this co-processed mannitol possessed favourable physical attributes including low hygroscopicity and compactibility. Two design-of-experiments (DoEs) were used to screen and optimise the placebo formulation. Xylitol and crospovidone concentrations were found to have the most significant impact on disintegration time (p < 0.05). Higher xylitol concentrations retarded disintegration. Avicel PH102 promoted faster disintegration than PH101, at higher levels of xylitol. Without xylitol, higher crospovidone concentrations yielded faster disintegration and reduced tablet friability. Lubrication sensitivity studies were later conducted at two fill loads, three levels for lubricant concentration and number of blend rotations. Even at 75% fill load, the design space plot showed that 1.5% lubricant and 300 blend revolutions were sufficient to manufacture ODTs with ≤ 0.1% friability and disintegrated within 15 s. This study also describes results using a modified disintegration method based on the texture analyzer as an alternative to the USP method.

Formulation and evaluation of sulfadimidine and trimethoprim tablets using wet granulation technique

The objective of this study was to develop tablet formulations of sulphadimidine sodium (SDD-Na) and trimethoprim (TMP), evaluate and compare the efficiency of some excipients such as: superdisintegrant - croscarmellose sodium (Ac-Di-Sol), silicon dioxide (Aerosil), lactose and microcrystalline cellulose (Avicel pH-101) as base excipients for physical tablets properties and increasing the dissolution rate of SDD-Na and TMP. All tablet formulations were prepared by wet granulation process. Dissolution properties such as DP 30,45,60 (percent of drug dissolved at 30, 45 and 60 minutes), and dissolution rate constant value (K) were considered for comparing the dissolution results. The dissolution of SDD-Na and TMP from all examined tablet formulations followed Higuchi model kinetics with correlation coefficient (R) values from 0.984 to 0.995. The physical properties and in vitro drug release study revealed that tablets disintegration efficiency and drug dissolution depend on the amount of added disintegrant, the amount and presence of microcrystalline cellulose (Avicel) and lactose. Tablet formulation without addition of microcrystalline cellulose showed faster dissolution rate and shorter disintegration time as compared with that of tablets of formulations with microcrystalline cellulose. The results reveal that besides the type of diluents, the way of using superdisintegrant plays a major role in controlling disintegration of tablets. The portion of Ac-Di-Sol used as an intragranulary in the wet granulation process, is not as effective as that of the process of extragranulary addition. Tablets formulations F4 and F5 exhibited satisfactory friability, acceptable hardness, fulfilled the requirement for disintegration time for compressed tablets, and met the acceptable specifications with regard to drug release properties.