Avicel PH Research Articles

Preparation and evaluation of diclofenac sodium orally disintegrating tablets

Abstract Orally disintegrating tablets (ODTs) are dosage forms which disintegrate in mouth within seconds without need of water. This type of quality in dosage form can be attained by addition of different varieties of excipients. Pharmaburst™ 500 is a co-processed excipient system which allows rapid disintegration and low adhesion to punches. The aim of the present study was to develop and evaluate 25 mg diclofenac sodium ODTs (orodispersible tablets) batches by direct compression method at different compression forces 10 kN (F1) and 20 kN (F2) and directly compressible excipients used in different ratio (Avicel PH 102, magnesium stearate and coprocessed excipient Pharmaburst™ 500, 70% and 80% w/w). The obtained batches were analyzed for appearance, tablet thickness, uniformity of weight, hardness, friability, disintegration time, and non-compendial methods (wetting time). Co-processed Pharmaburst™ 500 excipient 70% used for sodium diclofenac ODT obtaining determined good results for quality control tests evaluation.

Enabling the Tablet Product Development of 5-Fluorocytosine by Conjugate Acid Base Cocrystals

5-Fluorocytosine (FC) is a high-dose antifungal drug that challenges the development of a tablet product due to poor solid-state stability and tabletability. Using 2 pharmaceutically acceptable conjugate acid base (CAB) cocrystals of FC with HCl and acesulfame, we have developed commercially viable high loading FC tablets. The tablets were prepared by direct compression using nano-coated microcrystalline cellulose Avicel PH105 as a tablet binder, which provided both excellent tabletability and good flowability. Commercial manufacturability of formulations based on both CAB cocrystals was verified on a compaction simulator. The results from an expedited friability study were used to set the compaction force, which yielded tablets with sufficient mechanical strength and rapid tablet disintegration. This work demonstrates the potential value of CAB cocrystals in drug product development.

Silicified microcrystalline cellulose based pellets and their physicochemical properties

ABSTRACTSilicified microcrystalline cellulose (SMCC), Prosolv SMCC 50 was used as spheronization aid to manufacture pellets by extrusion and spheronization. Different ratios of SMCC to lactose were used to manufacture pellets using appropriate levels of water as liquid binder. Avicel PH101 based pellets were also manufactured for comparison of their physical properties. The ratio of liquid binder to spheronization aid was critical to produce pellets of desired size and shape. Extrudates composed of 20% aid could withstand only smaller spheronization force in order to be shaped into pellets. The successful products fulfilled the quality of pellets such as narrow size distribution and spherical in shape. The highest surface tensile strength was observed in pellets with equal ratio of lactose to SMCC while pellets having 20% aid disintegrated rapidly within 15 min. Furthermore, Prosolv SMCC 50 based pellets possessed a stronger surface tensile strength when compared with Avicel PH101 based pellets. In conclusion, Prosolv SMCC 50 has showed to be a good spheronization aid for extrusion and spheronization when used in the range of 20 to 80% content. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43829.

FORMULATION DEVELOPMENT, OPTIMIZATION & IN VITRO CHARATERIZATION OF LIQUISOLID COMPACTS OF AN OXICAM DERIVATIVE

The rationale of the current research was to investigate the in vitro dissolution properties of poorly water soluble piroxicam by utilizing liquisolid technology. Dissimilar liquisoli compacts were formulated using a factorial design to estimate the required quantities of powder and liquid ingredients to fabricate adequately flowable and compressible admixture. About 16 different formulations were developed using factorial design with carriers Neusilin (Magnesium aluminometasilicate)Â and Avicel PH 102, binder PVP K-30 and vehicle PEG-400 as independent variables and Aerosil 200 is used as coating material. The In-vitro drug release from the LSC has used a dependent variable. The empirical method by Spireas and Bolton was applied to calculate the amounts of carrier and coating materials and obtained the improved flow characteristics and hardness by changing the proportion of carrier and coating materials. Liquid solid compacts were fabricated and evaluated for their tabletting properties. Fourier transform infrared (FTIR) analysis, differential scanning calorimetry (DSC) and X- ray powder diffraction (XRPD) were performed. The FTIR spectra showed disappearance of the characteristic absorption band of piroxicam (3338.78 cm-1) in liquisolid formulations which might be attributed to the formation of hydrogen bonding between the drug and liquid vehicle; this resulted in drug dissolution enhancement. A 23 factorial design is used and developed liquid soild compacts using Neusilin LSCN1 to LSCN8 and Avicel PH 102 LSCA1 to LSCA8. The physicochemical characterization of all formulations exhibited well within the specification limits with respect to weight variation, hardness, friability and content uniformity. Â The In-vitro drug release from these liquid soild compacts was evaluated in 0.1 N HCl and the optimized formulation LSCA8 was compared with pure drug (capsule) and physical mixture (tablet). The release studies suggested that the liquisolid tablets outcome in higher release profile than pure active pharmaceutical ingredient and physical mixture due to enhance in surface and wetting properties of the active pharmaceutical ingredient. Liquid solid compacts technique confirmed the enhanced dissolution rate of oxicam derivative, which in turn promotes in enhancing bioavailability. Keywords: Piroxicam, Factorial design, Solubility, Dissolution rate, Avicel PH 102

Multiple-unit tablet of probiotic bacteria for improved storage stability, acid tolerability, and in vivo intestinal protective effect

The aim of this study was to formulate probiotics-loaded pellets in a tablet form to improve storage stability, acid tolerability, and in vivo intestinal protective effect. Bacteria-loaded pellets primarily prepared with hydroxypropyl methylcellulose acetate succinate were compressed into tablets with highly compressible excipients and optimized for flow properties, hardness, and disintegration time. The optimized probiotic tablet consisted of enteric-coated pellets (335 mg), microcrystalline cellulose (Avicel PH102, 37.5 mg), and porous calcium silicate (25 mg) and allowed whole survival of living bacteria during the compaction process with sufficient tablet hardness (13 kp) and disintegration time (14 minutes). The multiple-unit tablet showed remarkably higher storage stability under ambient conditions (25°C/60% relative humidity) over 6 months and resistance to acidic medium compared to uncoated strains or pellets. Repeated intake of this multiple-unit tablet significantly lowered plasma level of endotoxin, a pathogenic material, compared to repeated intake of bare probiotics or marketed products in rats. These results, therefore, suggest that the multiple-unit tablet is advantageous to better bacterial viability and gain the beneficial effects on the gut flora, including the improvement of intestinal barrier function.

Production of Starch Based Bioplastic from Cassava Peel Reinforced with Microcrystalline Celllulose Avicel PH101 Using Sorbitol as Plasticizer

The production of starch based bioplastics from cassava peel reeinforced with microcrystalline cellulose using sorbitol as plasticizer were investigated. Physical properties of bioplastics were determined by density, water uptake, tensile strength and Fourier Transform Infrared Spectroscopy. Bioplastics were prepared from cassava peel starch plasticized using sorbitol with variation of 20; 25; 30% (wt/v of sorbitol to starch) reinforced with microcrystalline celllulose (MCC) Avicel PH101 fillers with range of 0 to 6% (wt/wt of MCC to starch). The results showed improvement in tensile strength with higher MCC content up to 9, 12 mpa compared to non-reinforced bioplastics. This could be mainly attributed to the strong hydrogen bonds between MCC and starch. On the contrary, the addition of MCC decreased the elongation at break, density and water uptake. Fourier Transform Infrared Spectroscopy showed the functional groups of bioplastics, which the majority of O-H groups were found at the bioplastics with reinforcing filler MCC that represented substantial hydrogen bonds. The highest tensile strength value was obtained for bioplastic with MCC content 6% and sorbitol content 20%. With good adhesion between MCC and starch the production of bioplastics could be widely used as a substitute for conventional plastics with more benefits to the environment.

Comparison of Conventional and Lignin-Rich Microcrystalline Cellulose

Three microcrystalline cellulose (MCC) samples were manufactured from bleached and unbleached softwood kraft pulp, and their properties were compared to those of the commercial MCC, Avicel PH-101. One of the produced samples retained a large portion of lignin (10.3%), while the two others retained only some. The physical, chemical, thermogravimetric, and molecular properties were analyzed. The presence of lignin caused a substantial effect on the thermogravimetric and chemical properties of the MCC, as well as on its surface characteristics. The lignin-containing sample degraded at lower temperatures, and its UV Raman spectra had a high intensity aromatic band (1600 cm-1) arising from the lignin. X-ray photoelectron spectroscopy confirmed a high surface lignin coverage (40%) in this specimen only. Particle size and BET surface area measurement results varied in some limits between MCCs, while the cellulose crystallinity index showed almost equal values between 0.82 and 0.84. This work introduces a new wood-based product, the lignin-containing MCC, comparable in properties to the wide-marketed Avicel.

The application of terahertz pulsed imaging in characterising density distribution of roll-compacted ribbons

Roll compaction is a commonly used dry granulation process in pharmaceutical, fine chemical and agrochemical industries for materials sensitive to heat or moisture. The ribbon density distribution plays an important role in controlling properties of granules (e.g. granule size distribution, porosity and strength). Accurate characterisation of ribbon density distribution is critical in process control and quality assurance. The terahertz imaging system has a great application potential in achieving this as the terahertz radiation has the ability to penetrate most of the pharmaceutical excipients and the refractive index reflects variations in density and chemical compositions. The aim of this study is to explore whether terahertz pulse imaging is a feasible technique for quantifying ribbon density distribution.Ribbons were made of two grades of microcrystalline cellulose (MCC), Avicel PH102 and DG, using a roll compactor at various process conditions and the ribbon density variation was investigated using terahertz imaging and section methods. The density variations obtained from both methods were compared to explore the reliability and accuracy of the terahertz imaging system. An average refractive index is calculated from the refractive index values in the frequency range between 0.5 and 1.5THz. It is shown that the refractive index gradually decreases from the middle of the ribbon towards to the edges. Variations of density distribution across the width of the ribbons are also obtained using both the section method and the terahertz imaging system. It is found that the terahertz imaging results are in excellent agreement with that obtained using the section method, demonstrating that terahertz imaging is a feasible and rapid tool to characterise ribbon density distributions.

Formulation for Enhancement of Rate of In Vitro Drug Release Profiles of Poorly Soluble Rilpivirine Hydrochloride by Spray Drying Technique

Aim: The aim of the present research work was to enhance the rate of in vitro drug release profiles of poorly soluble Rilpivirine Hydrocloride (RH) by Spray drying technique. Rilpivirine is a non-nucleoside reverse transcriptase inhibitor of human immunodeficiency virus type-1 (HIV-1). Method: RH is belongs to BCS class-II. It is insoluble in water and practically insoluble across the pH range of 1 – 7.5. One of the major concerns with the formulation of RH is its poor solubility, which results into poor bioavailability after oral administration. Spray drying technique has been proven to be an efficient technique for conversion of poorly soluble crystalline form into highly soluble amorphous form and make it useful for formulating lab scale batches to commercial batches. Hence, Spray drying technique was chosen for reducing the % of crystallinity / or converting crystalline form into highly soluble amorphous form by spray drying technique. The organic dispersion comprising RH, hydrophilic carriers like Soluplus / Kollidon VA64 / Kolliphor SLS / Kolliphor P407 / Kollidon 30 at different ratios along with finer grade of microcrystalline cellulose (Avicel PH 105) was subjected to spray drying using Buchi spray dryer. Results & Discussion: The dissolution profiles of formulated product (RT2 & RT3) in FDA recommended dissolution media was compared against the dissolution profiles of corresponding innovator product. The rate of in vitro drug release was at faster and complete from test product as compared to Innovator product profiles i.e., EUDRANT™ 25 mg tablets. From the characterization of spray dried powder RSD8 by DSC and XRD concluded that % crystallinity of RH was reduced significantly. Conclusion: The obtained results suggested that Spray drying technique might be an efficacious approach in enhancing the therapeutic potential of Rilpivirine Hydrochloride.

Hot Melt Coating of Pellets for a Water Soluble Drug using Combination of Waxes

Waxes retards drug release from dosage form based on their lipophilic characteristics. In this study, the effect of hot melt spray coated Verapamil pellets with composition of stearic acid, carnauba wax; glyceryl monostearate and polyethylene glycol on drug release and release kinetics were investigated. The verapamil pellets containing 70% microcrystalline cellulose (Avicel PH101) were prepared by extrusion-spheronization technique and spray coated with molten wax at various ratios and thickness in a hot-melt spray coating instrument. In-vitro drug release was studied using test method for Extended Release tablets USP 24. The drug release was decreased with increase in stearic acid concentration and addition of 5% carnauba wax to stearic acid minimized initial burst release but it also retarded drug release. Glyceryl monostearate 30%w/w as release modifier at 20%w/w coating level provided desired drug release while PEG 6000 provided similar results at 2.5%w/w concentration. The plot of log fraction drug unreleased versus time showed a good linear relationship. Glycerol monostearate at 30%w/w as release modifier showed higher release rate in initial hours which declined with time and also R2 value for first order release kinetics was found to be nearest to one indicating drug release was dependent on initial concentration present in pellets. A zero order release profile was obtained from verapamil HCl sustained release pellets prepared by hot melt spray coating of stearic acid with sitable combination of carnuba wax and PEG 6000.

Looking at Adsorption of Cellulases NS 50013 onto Avicel PH 101 and Protobind 1000 through Isotherms and Thermodynamics

Understanding adsorption characteristics of cellulases can help to control the mechanism of adsorption of cellulases onto wheat straw. Desorption and reuse of cellulases is a way to decrease cost of production of bioethanol which can be perfected with knowledge of adsorption characteristics of cellulases. Adsorption of cellulases NS 50013 onto microcrystalline cellulose (Avicel PH 101) and wheat straw lignin (Protobind 1000) was studied in batch reactors. Protobind adsorbed twice the amount of cellulases as did Avicel PH 101 and the rate of adsorption was higher than that of Avicel PH 101. A comparison of three (most used) adsorption isotherms was conducted to see: i) A correlation between cellulases adsorbed and initial cellulases loading, ii) Is it a monolayer adsorption, iii) Adsorption capacities of the substrates. It was observed that Langmuir isotherm was a good representation of adsorption for both Avicel and Protobind on correlation coefficient of 0.9572 and 0.9880. The Gibbs free energy changes obtained by using van’t Hoff equation indicated that the adsorption was mainly spontaneous. However for Avicel, the process was spontaneous up to 220 μg.mL-1 and the spontaneity decreased with the cellulases concentration. For initial concentrations between 220 μg.mL-1 and 250 μg.mL-1 the cellulases adsorption process became non-spontaneous. While ΔG was quite opposite for Protobind, as it was non spontaneous at 100 μg.mL-1 and for further increase in concentration it was found spontaneous till 262 μg.mL-1. Among all three, Langmuir adsorption isotherm appeared to be the best represented of the cellulosic adsorption pattern. Hence, implying homogenous, monolayer adsorption. The reversible part of Langmuirian adsorption theory is in question in recent enzymatic literature therefore, a detailed study on desorption has been suggested by authors.

Self microemulsefying and non-self microemulsefying liquisolid tablet of felodipine

Liquisolid formulation involves dissolution or dispersion of the drug in a liquid before formulation of solid dosage form using solid adsorbent as a carrier. The liquid component usually utilizes simple solvent system. Self emulsifying liquids can provide another alternative liquid for enhanced dissolution. The objective of this work was to develop and evaluate non-self emulsifying and self emulsifying liquisolid tablet for enhanced dissolution rate of felodipine. The former utilized polyethylene glycol 400 which was the best solvent and the later employed a mixture of castor oil with labrasol and transcutol as self emulsifying system. A mixture of avicel PH 102 and aerosil 200 was used as solid adsorbent with croscarmellose being used as superdisintegrent. Formulation of the drug as liquisolid tablets enhanced the dissolution rate compared with the standard tablet prepared using the unprocessed drug powder with the same tablet excipients. The self emulsifying tablet showed faster release pattern compared with the non-self emulsifying tablet. The thermal analysis studies indicated the presence of the drug in a solution form in the tablet formulations. In conclusion liquisolid tablet formulation can enhance the dissolution rate of felodipine with self emulsifying liquid system being more efficient.

Effect of roll compactor sealing system designs: A finite element analysis

In the pharmaceutical industry, the roll compaction is part of the dry granulation process, densifying fine powders into ribbons that will be later milled to produce granules with good flowability for subsequent die compaction process. Roll compactors are constructed with a sealing system, limiting the loss of powder from the sides. However, the sealing system may result in unwanted non-uniformity of the ribbon's properties. In this work, a 3D Finite Elements Method (FEM) modeling is used to analyze the roll compaction process and the effect of sealing system designs on the compacted ribbon's density distribution. A density dependent Drucker–Prager Cap (DPC) constitutive model for microcrystalline cellulose (Avicel PH-101) was calibrated and implemented in Abaqus/Explicit. Two different FEM models were investigated, one with a fixed side sealing called cheek plates and another where the side sealing is integrated with the bottom roll called rimmed-roll. Both numerical and experimental results clearly show the non-uniform roll pressure and density distribution for the cheek plates assembly, whereas the rimmed-roll shows an overall more uniformly distributed resultant pressure and density distribution. These results demonstrate the capability of FEM modeling to provide insight and help achieving a better understanding of the roll compaction process.

Improved Dissolution Properties of Ketoconazole through Application of Liquisolid Techniques

In present investigation liquisolid compact technique is investigated as a tool for enhanced dissolution of poorly water-soluble drug Ketoconazole. The liquisolid tablets were formulated with liquid medications, namely Propylene Glycol (PG) drug concentrations, 60% w/w, 70% w/w and 80% w/w. Avicel pH102 was used as a carrier material, Aerosil 200 as a coating material and Sodium starch glycollate as a super-disintegrant. Quality control tests, such as uniformity of tablet weight, uniformity of drug content, tablet hardness, friability test, disintegration and dissolution tests were performed to evaluate prepared tablets. For further confirmation of results the liquisolid compacts were evaluated by XRD and FTIR studies to prove that, solubility of Ketoconazole has been increased by liquisolid compact technique. From the results obtained, it was be speculated that such systems exhibit enhanced drug release profiles due to increased wetting properties and surface of drug available for dissolution. As liquisolid compacts demonstrated significantly higher drug release rates, in PG as compared to directly compressible tablets and conventional wet granulation, we lead to conclusion that it could be a promising strategy in improving the dissolution of poor water soluble drugs and formulating immediate release solid dosage forms.

Enhancement of the Oral Bioavailability of Fexofenadine Hydrochloride via Cremophor(®) El-Based Liquisolid Tablets.

The current work aimed to develop promising Fexofenadine hydrochloride (FXD) liquisolid tablets able to increase its oral bioavailability and shorten time to reach maximum plasma concentrations (Tmax). Eighteen liquisolid powders were developed based on 3 variables; (i) vehicle type [Propylene glycol (PG) or Cremophor(®) EL (CR)], (ii) carrier [Avicel(®) PH102] to coat [Aerosil(®) 200] ratio (15, 20, 25) and (iii) FXD concentration in vehicle (30, 35, 40 %, w/w). Pre-compression studies involved identification of physicochemical interactions and FXD crystallinity (FT-IR, DSC, XRD), topographic visualization (SEM) and estimation of flow properties (angle of repose, Carr's index, Hausner's ratio). CR-based liquisolid powders were compressed as liquisolid tablets (LST 9 - 18) and evaluated for weight-variation, drug-content, friability-percentage, disintegration-time and drug-release. The pharmacokinetics of LST-18 was evaluated in healthy volunteers relative to Allegra(®) tablets. Pre-compression studies confirmed FXD dispersion in vehicles, conversion to amorphous form and formation of liquisolid powders. CR-based liquisolid powders showed acceptable-to-good flow properties suitable for compaction. CR-based LSTs had appropriate physicochemical properties and short disintegration times. Release profile of LST-18 showed a complete drug release within 5 min. LST-18 succeeded in increasing oral FXD bioavailability by 62% and reducing Tmax to 2.16 h.

Quantifying effects of moisture content on flow properties of microcrystalline cellulose using a ring shear tester

In this work, we have quantified effects of moisture content, over the relative humidity (RH) range of 5–92% corresponding to 1.6–10.9% of water content, on flow properties of a grade of microcrystalline cellulose (Avicel PH102) using a ring shear cell. Several key powder flow parameters, including cohesion (τc), unconfined yield strength (fc), powder bulk density (ρb), flowability (ffc), and effective angle of internal friction (ϕe), were assessed. Powder flow properties deteriorated continuously with increasing RH, as shown by the higher fc and τc as well as lower ffc, under all stress conditions. With increasing RH, ρb increased and then decreased with a maximum at 20% RH. The ϕe initially increased, from 41 to 43 degrees, and then remained approximately constant from 20% to 92% RH. The deterioration in powder flow properties is caused by surface modification by moisture, which enhances particle-particle interaction strength. The knowledge obtained in this study is useful to achieving consistent properties of this important tablet excipient and formulations containing it.

Enhancement of Carvedilol Dissolution; Surface Solid Dispersion Versus Solid Dispersion

The aim of this work was to improve the aqueous solubility of carvedilol (CRV), poorly water soluble drug, using surface solid dispersion (SSD) technique. Drug was deposited over the surface of a hydrophilic, water-insoluble carrier (Avicel pH 101) by solvent evaporation. Pluronic F68 was added as a wetting agent to some formulations. To estimate the effect of SSD technique on drug dissolution, solid dispersions (SDs) of dug and Pluronic F68 were prepared by solvent evaporation. Pluronic F68 was selected due to its inhibiting effect to CYP3A4, an enzyme that contribute to hepatic metabolism of CRV. All formulations were characterized by in vitro dissolution studies; X-ray powder diffraction and scanning electron microscopy. SSD enhanced drug dissolution compared to pure drug. The addition of polymer to drug/carrier composite greatly improved drug dissolution compared to that without the polymer. Compared to SD, SSD showed a better drug release rate. X-ray diffraction indicated the complete reduction in drug crystallinity and the formation of the amorphous form in case of SSD, with limited reduction in crystallinity for SD. The obtained dissolution efficiency of SSD was comparable to that obtained from the marketed CRV product. The study thus presented a system capable of increasing the dissolution rate of CRV with a potential for increased oral bioavailability by inhibiting its pre-systemic metabolism as well.

Competence of raloxifene hydrochloride loaded liquisolid compacts for improved dissolution and intestinal permeation

The primary purpose of this research is to formulate raloxifene hydrochloride (RXH) loaded liquisolid compacts for improved dissolution behavior and intestinal permeation. Owing to their higher drug solubility, Cremophor® EL, Capmul PG-8 and Transcutol P were selected as suitable non-volatile liquid vehicles to develop desired formulations. The liquisolid formulations were obtained by allowing liquid vehicles with varying drug concentrations to get absorbed onto carrier and coating material taken at different ratios (R = 5; R = 10). Avicel PH 102 and Aerosil PH 200 displayed good liquid retention potential values confirming appropriate load factor and thus, resulting in liquisolid powders with good flow properties exemplifying their caliber as efficient solid carrier and coating materials in developing liquisolid compacts. FT-IR spectra illustrated no significant interaction between drug and carrier. The DSC and PXRD studies demonstrated the absence of crystalline form of drug in liquisolid powders. Further, the enhanced dissolution performance of RXH from liquisolid systems suggested the transformation of the drug to molecular/amorphous state. Ex vivo rat intestinal permeation studies revealed an improvement in drug absorption from formulation unraveling the ability of non-volatile liquid vehicles of liquisolid systems in enhancing the intestinal permeation of dissolution rate limited RXH.

Formulation and In Vitro and In Vivo Evaluation of Lipid-Based Terbutaline Sulphate Bi-layer Tablets for Once-Daily Administration

The objective of this study was to prepare and evaluate terbutaline sulphate (TBS) bi-layer tablets for once-daily administration. The bi-layer tablets consisted of an immediate-release layer and a sustained-release layer containing 5 and 10mg TBS, respectively. The sustained-release layer was developed by using Compritol®888 ATO, Precirol® ATO 5, stearic acid, and tristearin, separately, as slowly eroding lipid matrices. A full 4 × 2(2) factorial design was employed for optimization of the sustained-release layer and to explore the effect of lipid type (X 1), drug-lipid ratio (X 2), and filler type (X 3) on the percentage drug released at 8, 12, and 24h (Y 1, Y 2, and Y 3) as dependent variables. Sixteen TBS sustained-release matrices (F1-F16) were prepared by melt solid dispersion method. None of the prepared matrices achieved the targeted release profile. However, F2 that showed a relatively promising drug release was subjected to trial and error optimization for the filler composition to develop two optimized matrices (F17 and F18). F18 which consisted of drug-Compritol®888 ATO at ratio (1:6 w/w) and Avicel PH 101/dibasic calcium phosphate mixture of 2:1 (w/w) was selected as sustained-release layer. TBS bi-layer tablets were evaluated for their physical properties, in vitro drug release, effect of storage on drug content, and in vivo performance in rabbits. The bi-layer tablets showed acceptable physical properties and release characteristics. In vivo absorption in rabbits revealed initial high TBS plasma levels followed by sustained levels over 24h compared to immediate-release tablets.

Recombinant Trichoderma harzianum endoglucanase I (Cel7B) is a highly acidic and promiscuous carbohydrate-active enzyme.

Trichoderma filamentous fungi have been investigated due to their ability to secrete cellulases which find various biotechnological applications such as biomass hydrolysis and cellulosic ethanol production. Previous studies demonstrated that Trichoderma harzianum IOC-3844 has a high degree of cellulolytic activity and potential for biomass hydrolysis. However, enzymatic, biochemical, and structural studies of cellulases from T. harzianum are scarce. This work reports biochemical characterization of the recombinant endoglucanase I from T. harzianum, ThCel7B, and its catalytic core domain. The constructs display optimum activity at 55 °C and a surprisingly acidic pH optimum of 3.0. The full-length enzyme is able to hydrolyze a variety of substrates, with high specific activity: 75 U/mg for β-glucan, 46 U/mg toward xyloglucan, 39 U/mg for lichenan, 26 U/mg for carboxymethyl cellulose, 18 U/mg for 4-nitrophenyl β-D-cellobioside, 16 U/mg for rye arabinoxylan, and 12 U/mg toward xylan. The enzyme also hydrolyzed filter paper, phosphoric acid swollen cellulose, Sigmacell 20, Avicel PH-101, and cellulose, albeit with lower efficiency. The ThCel7B catalytic domain displays similar substrate diversity. Fluorescence-based thermal shift assays showed that thermal stability is highest at pH 5.0. We determined kinetic parameters and analyzed a pattern of oligosaccharide substrates hydrolysis, revealing cellobiose as a final product of C6 degradation. Finally, we visualized effects of ThCel7B on oat spelt using scanning electron microscopy, demonstrating the morphological changes of the substrate during the hydrolysis. The acidic behavior of ThCel7B and its considerable thermostability hold a promise of its industrial applications and other biotechnological uses under extremely acidic conditions.