Silicified Microcrystalline Cellulose Research Articles

Novel Bioequivalent Tablet of Solifenacin Succinate Prepared Using Direct Compression Technique for Improved Chemical Stability.

We designed a bioequivalent tablet form of solifenacin succinate (SOL) with an improved storage stability using a direct compression (DC) technique. An optimal direct compressed tablet (DCT) containing an active substance (10 mg), lactose monohydrate, and silicified microcrystalline cellulose as diluents, crospovidone as a disintegrant, and hydrophilic fumed silica as an anti-coning agent was constructed by evaluating the drug content uniformity, mechanical properties, and in vitro dissolution. The physicochemical and mechanical properties of the DCT were as follows: drug content 100.1 ± 0.7%, disintegration time of 6.7 min, over 95% release within 30 min in dissolution media (pH 1.2, 4.0, 6.8, and distilled water), hardness > 107.8 N, and friability ~0.11%. The SOL-loaded tablet fabricated via DC showed an improved stability at 40 °C and RH 75%, exhibiting markedly reduced degradation products compared to those fabricated using ethanol or water-based wet granulation or a marketed product (Vesicare®, Astellas Pharma). Moreover, in a bioequivalence study in healthy subjects (n = 24), the optimized DCT offered a pharmacokinetic profile comparable to that of the marketed product, with no statistical differences in the pharmacokinetic parameters. The 90% CIs for the geometric mean ratios of the test to the reference formulation for the area under the curve and the maximum drug concentration in plasma were 0.98-1.05 and 0.98-1.07, respectively, and satisfied the FDA regulatory criteria for bioequivalence. Thus, we conclude that DCT is a beneficial oral dosage form of SOL with an improved chemical stability.

Flowability, binding and release property of “self-lubricating” microcrystalline cellulose

Microcrystalline cellulose (MCC) has been widely used as an excipient in tablets. Silicified microcrystalline cellulose (SMCC) has more application than MCC by using silicon dioxide (SiO2) as a lubricant. However, findings show that the silicon dioxide (SiO2) nanoparticle component is a physiological hazard. In our research, “self-lubricating” microcrystalline cellulose (MCC) was developed by a ball-milling treatment. Commercial MCC and undried MCC with 60% or 80% moisture content were ball-milled for 12 or 24 h. After ball milling, ellipsoid-like particles, with wrinkled surfaces, and a broader particle size distribution resulted in a balance between the flowability and tabletability of the treated MCC. FTIR and XRD analysis showed that cellulose Ⅱ was formed in the undried 60% moisture content MCC after ball milling for 12 or 24 h, which improved the burst disintegration ability of the tablets. In addition, the controlled-released MCC has also been developed. AFM patterns and the angle of repose showed a cohesion phenomenon and some bridges formed between particles of undried 80% moisture content MCC ball-milled for 12 h. Without adding SiO2, our MCC gained improved binding properties, a balance between flowability and tabletability, and a more useful controlled-released ability compared with commercial MCC and SMCC.

Design and Evaluation of Orally Dispersible Tablets Containing Amlodipine Inclusion Complexes in Hydroxypropyl-β-cyclodextrin and Methyl-β-cyclodextrin

The development of new orally dispersible tablets containing amlodipine (AML) inclusion complexes in hydroxypropyl-β-cyclodextrin (HP-β-CD) and in methyl-β-cyclodextrin (Me-β-CD) was studied. The methods of obtaining amlodipine and the physical and chemical properties of the inclusion complexes using the two cyclodextrins was investigated separately. Solid inclusion complexes were obtained by three methods: kneading, coprecipitation, and lyophilization, at a molar ratio of 1:1. For comparison, a physical mixture in the same molar ratio was prepared. The aim of the complexation process was to improve the drug solubility. As the lyophilization method leads to a complete inclusion of the drug in the guest molecule cavity, for both used cyclodextrins, these types of compounds were selected as active ingredients for the design of orally dispersible tablets. Subsequently, the formulation of the orodispersible tablets containing AML-HP-β-CD and AML-Me-β-CD inclusion complexes and quality parameters of the final formulation were evaluated. The results prove that F1 and F4 formulations, based on silicified microcrystalline cellulose, which contains insignificant proportions of very small or very large particles, had the lowest moisture degree (3.52% for F1 and 4.03% for F4). All of these demonstrate their porous structure, which led to good flowability and compressibility performances. F1 and F4 formulations were found to be better to manufacture orally dispersible tablets.

A Study of Compressibility, Compactability and Mucoadhesivity of Tableting Materials for Matrix Systems Based on Chitosan.

The objective of the present research is to evaluate directly compressible chitosan-based tableting materials for the formulation of mucoadhesive matrix tablets intended for targeted drug release to distal segments of the GIT. The influence of sodium alginate, hypromellose, and silicified microcrystalline cellulose (P90) on compressibility, compactability and lubricant sensitivity ratio was tested. Furthermore, the rheological properties of the hydrated surface layer of the matrix tablets and the mucoadhesion to a mucin substrate were analysed. Compressibility was evaluated using the energy profile of the compression process, compactability by means of the tensile strength of tablets, and lubricant sensitivity ratio was calculated to assess the sensitivity to lubricant. Addition of P90 to chitosan improved compressibility, which is demonstrated by the increase in the energy of plastic deformation and the higher tensile strength of tablets. P90 also significantly reduced the high lubricant sensitivity of chitosan. Presence of retarding components led to a decrease in Emax. All tested matrix tablets revealed a good mucoadhesion without a negative effect of P90 content. The viscosity of a gel layer on the surface of matrix tablets containing hypromellose was higher compared to those with sodium alginate. This was not reflected in the adhesive strength of the tablets. The formulated tableting materials combining chitosan and P90 are a suitable matrix for incorporation of an active ingredient, whose delayed release in the intestine can be achieved by the functionality of the chitosan-sodium alginate complex.

Effects of compaction pressure, speed and punch head profile on the ultrasonically-extracted physical properties of pharmaceutical compacts.

Despite a well-established manufacturing-process understanding, tablet quality issues are frequently encountered during various stages of drug-product development. Compact breaking force (tensile strength), capping and friability are among the commonly observed characteristics that determine the integrity, quality and manufacturability of tablets. In current study, a design space of the compaction pressure, compaction speed and head flat types is introduced for solid dosage compacts prepared from pure silicified microcrystalline cellulose, a popular tableting excipient. In the reported experiments, five types of head flat types at six compaction pressure levels and two compaction speeds were employed and their effects on compact mechanical properties evaluated. The mechanical properties of the tablets were obtained non-destructively. It is demonstrated these properties correlate well with compact porosity and tensile strength, thus their availability is of practical value. The reported mechanical properties are observed to be linearly sensitive to the tableting speed and compaction pressure, and their dependency on the head-flat profile, while clearly visible in the presented waveforms, was found to be nonlinear in the range of the parameter space. In this study, we detail a non-destructive, easy-to-use approach for characterizing the porosity and tensile strength of pharmaceutical tablets.

Interactions between Ibuprofen and Silicified-MCC: Characterization, Drug Release and Modeling Approaches

Analysis of the binding interactions of ibuprofen and silicified-microcrystalline cellulose (SMCC) has been undertaken. Co-processing of ibuprofen with SMCC was carried out by solid state ball milling, and aqueous state equilibration followed by freeze drying to investigate the effect of silicified-microcrystalline cellulose on ligand. Molecular docking study revealed that ibuprofen formed complex through hydrogen bond with microcrystalline cellulose (MCC) and silicon dioxide (SiO2); the binding energy between MCC and SiO2, and ibuprofen and SMCC were found as -1.11 and -1.73 kcal/mol respectively. The hydrogen bond lengths were varying from 2.028 to 2.056 Å. Interaction of Si atom of SMCC molecule with Pi-Orbital of ibuprofen has shown the bond length of 4.263 Å. Significant improvement in dissolution of ibuprofen has been observed as a result of interaction. Binary and ternary interactions revealed more stabilizing interactions with ibuprofen and SMCC compared to SMCC formation.

Effects of Surfactants on Itraconazole-Hydroxypropyl Methylcellulose Acetate Succinate Solid Dispersion Prepared by Hot Melt Extrusion III: Tableting of Extrudates and Drug Release From Tablets

Hydroxypropyl methylcellulose acetate succinate (HPMCAS) has gained popularity as a carrier for amorphous solid dispersion because of its ability to maintain drugs in supersaturated state after dissolution in aqueous media. In part I and II of this series of articles, we have demonstrated that amorphous solid dispersions containing HPMCAS may be prepared using surfactants as plasticizers to reduce processing temperature (Solanki et al., J Pharm Sci. 2019; 108:1453-65), where surfactants also increase dissolution rate and degree of supersaturation (Solanki et al., J Pharm Sci. 2019; 108: 3063-73). The present investigation was undertaken to develop melt extrudates of itraconazole-HPMCAS and itraconazole-surfactant-HPMCAS mixtures into tablets having tensile strength ≥2 MPa, where poloxamer 407 and d-α-tocopherol polyethylene glycol 1000 succinate were used as surfactants. Milled filaments were sieved to collect <212-μm particles, which were then compressed into tablets with different excipients (silicified microcrystalline cellulose [MCC], Avicel PH-102, dicalcium phosphate, lactose, and Starch 1500). Initial screening of various diluents showed that only silicified MCC and Avicel PH-102 could provide the target tensile strength of ≥2 MPa. Tabletability (tensile strength vs. compaction pressure), compressibility (porosity vs. compaction pressure), and compactibility (tensile strength vs. porosity) were then studied for tablet formulations. The desired tensile strength could be obtained at the diluent level of 50%-70%, where silicified MCC provided better hardness than Avicel PH-102. Tablets disintegrated in <2 min, and drug release from tablets was comparable to that of milled filaments.

New Perspective Enteric-Coated Tablet Dosage Form for Oral Administration of Ceftriaxone: In Vitro and In Vivo Assessments

Ceftriaxone (CTX) is a widely used injectable third-generation cephalosporin that exhibits broad-spectrum antibacterial activity. Unfortunately, the oral route of this drug suffers different encumbrances, such as instability in the upper part of the GIT and enzymatic degradation, as well as poor permeability. There is no reported tablet dosage form for this drug. In this respect, the authors investigated the possibility of developing an enteric-coated oral tablet of CTX that would be helpful for better patient compliance. The tablet consists of directly compressed core of CTX, citric acid (CA), sodium chloride (NaCl), and two biopolymers-chitosan (CH), a permeation enhancer, and silicified microcrystalline cellulose (SMCC), a wicking agent. Both biopolymers are naturally occurring polysaccharides that are biodegradable in the colon and able to incorporate acid labile drugs. CA is a pH modulator to protect CTX from protease enzymes, while NaCl is a translocation enhancer that helps drug penetration. The enteric coat of the core was shellac (SH) with plasticizer glycerol tristearate (GTS) and CA that was applied by direct compression (dry coating). The solventless heat curable coat resulted in an enteric-coated tablet that complies with the USP pharmacopeia. The optimized formula was further subjected to in vitro release and stability studies, as well as ingredient compatibility. In vivo oral bioavailability of the enteric-coated tablets in rabbits gave promising results (absolute bioavailability of about 80%). Synergistically, all ingredients together augmented oral bioavailability of CTX. This developed formula could be a perspective delivery system for those drugs intended to be absorbed from the colon such as peptides and peptide-like drugs.

Measuring bulk density variations in a moving powder bed via terahertz in-line sensing

Monitoring the relative density of static or moving powder inside a process line is essential for manufacturing high-quality products. The aim of this study was to predict density variations in a moving powder bed using terahertz reflection technology. We systematically investigated three grades (varying true density and particle size) of two materials: lactose and silicified microcrystalline cellulose (SMCC). These six powders specifically differ in their compressibility, which can be applied to assess the sensitivity and applicability of our method. The powders were filled into a round container, and terahertz reflection measurements were acquired continuously during the container’s rotation. The setup allowed to adjust the relative density by compacting the powders into specific powder bed heights. Each powder was compacted to various relative densities (compression pressures up to 100 kPa). We calculated the surface refractive index based on the in-line terahertz measurements acquired during rotation, which has a linear dependence on the relative density of the powder. This was confirmed by correlating the refractive index values with the theoretical relative densities based on the bulk and true densities of the powder. The coefficient of determination (R2) was larger than 0.962 (Lactohale 100) for all six powders, with the highest coefficients for Lactohale 220 (R2 = 0.996) and SMCC 50 LD (R2 = 0.995). The results suggest that the proposed method can resolve relative densities averaged across the powder bed that are as small as 0.3% (Lactohale 100). The high acquisition rate of the terahertz system (15 Hz) made it possible to determine the powder density in 230 positions uniformly distributed throughout the container, facilitating the investigation of the relative density uniformity in the container as a function of the powder bed height. It was observed that SMCC powders undergo a smaller change in the relative density variations upon compaction than the lactose powders. Moreover, the relative density maps clearly indicate local density differences in the powder bed for all powders. The relative density variations that were introduced by packing of the container prevailed throughout the compaction process for all samples with the exception of Lactohale 220. The presented approach allows a precise resolution of the spatial distribution of relative density, which facilitates an in-depth analysis of powder behavior upon compaction.

CAUSE-EFFECT RELATIONS AND OPTIMIZATION OF TABLET CONTAINING EUCOMMIA ULMOIDES AND GARDENIA JASMINOIDES SPRAY-DRIED EXTRACTS

Objective: The E. ulmoides and G. jasminoides (EG) tablets containing 67 mg E. ulmoides spray-dried extract (ESE) and 173 mg G. jasminoides spray-dried extract (GSE) were prepared by employing the direct compression method. Due to the poor flowability and compressibility of the two spray-dried extracts, various excipients were added at different ratios so that the blends can be compressed into tablets with the required standards. This study aimed at the cause-effect relations and optimization of the EG tablet formulation.Methods: Different diluents including dibasic calcium phosphate anhydrous (DCPA), silicified microcrystalline cellulose (SMCC), spray-dried lactose (SDL) and the active ingredients (blend of ESE and GSE at the ratio of 67:173, w/w) were separately investigated their own physical properties. The binary mixtures of the active ingredients with different ratios of DCPA, SMCC, and SDL were evaluated their flowability. D-optimal design based on three independent variables (% DCPA, % croscarmellose sodium (CCS) and % SMCC) was applied to evaluate the cause-effect relations and optimize the EG tablet formulation. The weight variation, disintegration time, hardness and friability were investigated as four dependent variables.Results: The flowability of the powders was found to be affected by the particle size distribution, particle shape and density. The three diluents could significantly improve the flowability of the active ingredients. All independent variables had significant effects on the dependent variables. An increase in % SMCC reduced the weight variation, hardness and increased the friability of tablets. Disintegration time was found to be in the negative relations with % CCS. The tablet hardness was in positive relations with % DCPA. The optimized EG tablet formulation composed of 9 % DCPA (w/w), 35 % SMCC (w/w), and 14 % CCS (w/w) of the excipient blend. The weight variation, disintegration time, hardness and friability of the optimized EG tablets were found to be 1.8 %, 11.7 min, 61.4 N, and 0.5 %, respectively.Conclusion: The ESE and GSE could be formulated into tablet by using direct compression method. The cause-effect relations and optimization of EG tablet formulation were studied and reported for the first time.

Evaluation of non-crystalline cellulose as a novel excipient in solid dose products

Objective: The objective of this study was to evaluate non-crystalline cellulose (NCC) as a novel tablet excipient in solid oral dosage forms in comparison with microcrystalline cellulose (MCC) and silicified microcrystalline cellulose (Prosolv®, SMCC).Significance: MCC, although a widely used tablet excipient, has diasdvantages in terms of its low dilution potential for potent drugs, and sensitivity to lubricant and moisture. SMCC, a modified version of MCC, has improved tablet compression properties. However, SMCC is expensive and also affects the moisture sorption and particle deformation during compression leading to increased tensile strength and tablet hardness. NCC was found to be similar to SMCC in its performance as a tablet excipient and thus can serve as a cheaper alternative to SMCC.Methods: Scanning electron microscopy (SEM), X-ray diffrectometry (XRD), and differential scanning calorimetry (DSC) analyses were performed on NCC, MCC, and SMCC. Further, out-of-the die Heckel, Kawakita compact densification and stress-strain analyses were performed to evaluate their compaction and compressibility properties. Various compendial and non-compendial tests were performed to to determine the flow properties of materials. Dissolution studies were performed using amlodipine besylate as a marker drug.Results: It was found that NCC has similar or even better flow properties and compactibility than MCC due to its porous and amorphous structure whereas it had similar properties as SMCC.Conclusions: Based on the data, it can be concluded that NCC can serve as a cheaper and better alternative to MCC as excipient in solid dosage forms.

The impact of polymers on 3D microstructure and controlled release of sildenafil citrate from hydrophilic matrices

Sildenafil citrate has short biological half-life in humans. Thus, matrix tablets of controlled release were designed and prepared by compaction on the basis of hydrophilic polymers, i.e. HPMC, sodium alginate, carbomer, poloxamer and their mixtures. The impact of these polymers on sildenafil release in vitro and its pharmacokinetics in vivo was evaluated. Since drug release rate from hydrophilic matrices can be govern by the porosity of the matrix, the microstructure of tablets was studied using X-ray microcomputed tomography. 3D network of either open (percolating) or closed (non-percolating) pores was reconstructed. The tortuosity and the diameter of both kinds of pores were determined. Their spatial distribution within the matrix was analyzed in linear and radial direction. Polymer-dependent characteristics of the open pores (Ø > 2 μm) architecture was shown. The release profiles of sildenafil from matrix tablets fitted to Korsmeyer-Peppas model (r2: 0.9331–0.9993) with either Fickian diffusion or anomalous transport involved. Mean dissolution time (MDT) from tablets made of HPMC, carbomer or a mixture of HPMC and sodium alginate (2:1) was ca. 100 min, which was more than twelve times longer as compared to matrices prepared of silicified microcrystalline cellulose (MDT = 8 min). MDT correlated with the number of the open pores (Pearson's r = 0.94). Sustained release of sildenafil from ground carbomer tablets reflected in the slow absorption of the drug (tmax = 5.0 ± 1.2 h) in vivo and the relative bioavailability of 151%. Interestingly, the relative bioavailability of sildenafil from binary matrices composed of HPMC and sodium alginate (2:1) was almost four times higher than that of sildenafil alone.

Formulation, swelling and dissolution kinetics study of zein based matrix tablets

This study has investigated the potential use of zein protein from corn as a pharmaceutical excipient for formulation of oral controlled-release matrices. SMCC (silicified microcrystalline cellulose)-Prosolv® 90, SMCC HD-Prosolv® 90 HD, Avicel® PH 102 and Mannitol 60 were evaluated as co-excipients to improve the processability of zein powder. Zein/SMCC-Prosolv® 90 blend had the best flowability and tabletability. Tablets with tramadol hydrochloride, zein and SMCCProsolv® 90 were prepared by direct compression. Drug release from the tablets was measured by dissolution testing. The dissolution profiles obtained were compared using the dissolution efficiency (DE) and were fitted to the Korsmeyer–Peppas equation. Controlled drug release, governed by anomalous (non-Fickian) drug transport, was obtained over the test duration. Drug release rate and mechanism were dependent on formulation parameters, such as tablet hardness, zein/SMCC ratio and drug loading, as well as medium pH. Dynamics of tablets swelling correlated well with drug release rate and mechanism, with faster drug release and greater contribution of polymer relaxation being obtained at increased swelling. In conclusion, the present work has shown that zein/SMCC based matrix formulation can be used as a new platform for oral-controlled drug delivery which can be easily customized by adjusting formulation parameters. The use of this formulation could be attractive for customers and manufacturers who prefer to avoid synthetic or chemically modified excipients.

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.

Optimization of composition and technology for tablets containing aspen bark extract

Summary. Influence of quantitativefactorsof basic quality parameters has been investigated for tabletscontainingextractofaspenbark, receivedbydirect pressingmethodand mathematicalplanningof experiment.To set the optimal composition of tablets containingaspen bark extract the proportion ofProsolv 90, Ludiflash and Polyplasdone XL 10 has been studied. The relationship between the studied factors and parameters of tablets’ regression models has been described. As a result tablets containing aspen bark extractwith mentioned above formula match necessary pharmaco-technological parameters of State Pharmacopoeia of Ukraine.Introduction.Peptic and duodenal ulcer are serious problems in modern medicine. According to statistics this disease is found in 12,83 % of the adult population in Ukraine [1]. Among the remedies for treatment and prevention of peptic ulcers we can find herbal medicines that may be used in the treatment of pre-peptic conditions and during an acute period as a means of adjuvant therapy in combination with strong remedies [2]. An antacid, cytoprotective, anti-inflammatory and reparative actions of aspen bark extract were proved by the researches of domestic and foreign scientists [3, 4].Previously, we researched the mutual influence of excipients on the main indicators of quality of aspen bark extract tablets obtained by direct compression method. Due to these researches the best excipientshave been selected. It is necessary to establish the optimal quantitative proportion of excipients in order to obtain the tablets with suitable parameters that satisfy the requirements of the State Pharmacopoeia of Ukraine (SPU) [5, 6].Rational selection of excipients requires wide range of studies to obtain the optimal composition of the tablets containing aspen bark extract. Using mathematical planning of the experiment gives the possibility to reduce the number of experiments and to obtain the most detailed results of researches about effects of excipients on the basic parameters of tablet quality.The aim of investigation.In the previous stages of the experiment, we studied the effect of quantitative factors on pharmaco-technological parameters of tablets. To further study were selected Prosolv 90, Ludiflash and Polyplasdone XL 10.The aim of investigation was to set and study the proportion of excipients selected for developing optimal formula of tablets containing aspen bark extract.Materials and methods.The tablets based on aspen bark extract, obtained by direct compression method, have beenselected as research object. In the development of technology and tablet form,dry aspen bark extract, obtained by the Department of Pharmacognosyof the National University of Pharmacy,has been used [7]. The dry aspen bark extract is hygroscopic fine powder with particles of anizodiametric shape.Namely, from the group of samples of microcrystalline cellulose (MCC) – Prosolv 90 (Silicified MCC, manufactured by JRS Pharma GMBH &amp; Co KG., Germany), from the group structure-based substances sugars – Ludiflash (combination of mannitolCrospovidone, Povidone and polyvinyl acetate, manufactured by BASF Corp., USA) and from the group of disintegrants – Polyplasdone XL 10 (homopolymer of vinyl pyrrolidone, manufactured by manufactured by Ashland Inc., USA). At establishment of optimal composition of the tablets based on aspen bark extract three excipientsinfluence, and also their correlation in composition of tabletshas been studied [8].Results and discussion.The optimal formula of selected excipients has been set and their proportions in tablet dosage form at the shorter intervals have beendetermined. The study of each researched factor has been carried out according to 5 levels. As a result of studies we found the optimal number of excipients for tablet formula: Prosolv 90 – 0,054 g, Ludiflash – 0,03 g, Polyplasdone XL 10 – 0,025 g, MCC 102 – 0,0835 g, magnesium stearate – 0,0025 g in one unit of dose medication. As a result tablets of aspen bark extract with mentioned above formula have necessary pharmaco-technological parameters that meet the requirements of SPU: resistance to crushing – 130 H, abrasion – 0,04 % mass uniformity of tablets – ± 2,85%, disintegration – 6 min [9].ConclusionsDue to mathematical planning the quantitative impact of significant excipients on pharmaco-technological parameters of tablets based on aspen bark extract: Prosolv 90, LudiflashтаPolyplasdone XLhave been studied.Due to the regression analysis optimal composition of tablets based on aspen bark extract : dry aspen bark extract – 0,05 g, Prosolv 90 – 0,054 g, Ludiflash – 0,03 g, Polyplasdone XL 10 – 0,025 g, MCC 102 – 0,0835 g,Neusilin US 2 – 0,0025 g, talc –0,0025 g, magnesium stearate – 0,0025 ghas been determined. As a result tablets of aspen bark extract with mentioned above formula have necessary pharmaco-technological parameters that meet the requirements of SPU.

POlmesartan medoxomil surface solid dispersion-based orodispersible tablets: formulation and in vitro characterization

This work aims to improve the dissolution of the poorly water soluble drug olmesartan medoxomil by using the surface solid dispersion (SSD) technique. Insoluble carriers, namely Avicel PH102, Aerosil 200, silicified microcrystalline cellulose, Lycatab, Starlac, sodium starch glycolate (SSG), and Kyron T-314, were used at three different drug: carrier ratios (1:1,1:5, and 1:9 w/w) to prepare SSDs by solvent evaporation method. SSD18 consisting of drug:SSG at 1:9 ratio and SSD20 consisting of drug:Kyron T-314 at 1:5 ratio showed the highest enhancement in the dissolution rate and efficiency compared to the plain drug and the physical mixture. The selected dispersion was formulated into orodispersible tablets (ODTs) by using four different disintegrants. F3 DC ODT (consisting of SSD20 and 5 % crospovidone) and F6 DC ODT (consisting of SSD18 and no disintegrant) exhibited low in vitro disintegration time and high percentage of olmesartan medoxomil dissoluted within 10 min.

Development, Characterization and Permeability Assessment Based on Caco-2 Monolayers of Self-Microemulsifying Floating Tablets of Tetrahydrocurcumin

Novel self-microemulsifying floating tablets were developed to enhance the dissolution and oral absorption of the poorly water-soluble tetrahydrocurcumin (THC). Their physicochemical properties and THC permeability across Caco-2 cell monolayers were assessed. The self-microemulsifying liquid containing THC was adsorbed onto colloidal silicon dioxide, mixed with HPMC, gas-generating agents (sodium bicarbonate and tartaric acid), lactose and silicified-microcrystalline cellulose and transformed into tablets by direct compression. The use of different types/concentrations of HPMC and sodium bicarbonate in tablet formulations had different effects on the floating characteristics and in vitro THC release. The optimum tablet formulation (F2) provided a short floating lag time (∼23 s) together with a prolonged buoyancy (>12 h). About 72% of THC was released in 12 h with an emulsion droplet size in aqueous media of 33.9±1.0 nm while that of a self-microemulsifying liquid was 29.9±0.3 nm. The tablet formulation was stable under intermediate and accelerated storage conditions for up to 6 months. The THC released from the self-microemulsifying liquid and tablet formulations provided an approximately three- to fivefold greater permeability across the Caco-2 cell monolayers than the unformulated THC and indicated an enhanced absorption of THC by the formulations. The self-microemulsifying floating tablet could provide a dosage form with the potential to improve the oral bioavailability of THC and other hydrophobic compounds.

Tableting functionality evaluation of Prosolv Easytab in comparison to physical mixtures of its individual components

Prosolv Easytab is a recently introduced all-in-one excipient for direct compression. The aim of this work was to compare the compaction and dissolution functionalities of Prosolv Easytab versus equivalent physical mixtures of microcrystalline cellulose (MCC) or silicified microcrystalline cellulose (Prosolv SMCC) with complementary excipients. Lutrol F68 was used as a free flowing and poorly compactable model material for the comparison of the compaction functionality, and carbamazepine was used as a poorly soluble model drug for the investigation of the dissolution rate and dissolution stability after storage under accelerated stability conditions. Results showed that Prosolv Easytab produced comparable compactibility, dissolution and dissolution stability to its analogous physical mixtures based on MCC or Prosolv SMCC. The current findings suggest that Prosolv Easytab is functionally equivalent to physical mixture of its components, with obvious advantages regarding simplicity of manufacture and the potential masking of undesirable properties of individual components.

Hypolipidemic applications of microcrystalline cellulose composite synthesized from different agricultural residues

Microcrystalline cellulose was prepared from bean hull, rice straw and rice hull. The use of rice hull and rice straw pulp in different proportions as a source of silica to prepare silicified microcrystalline cellulose was investigated. Preparations of microcrystalline cellulose–potato starch composites with different potato starch concentrations were performed. All samples were characterized through various techniques. Physical and mechanical properties of the prepared tablets were tested. The biological activities of one composite was tested in a hyperlipidemic rat model and compared to orlistat to assess its antilipidemic potential. This composite exhibited remarkable antilipidemic effect with decreased insulin sensitivity.

Comparison of traditional and novel tableting excipients: Physical and compaction properties

Context: Novel tableting excipients are continuously developed and advertised with superior flow and compaction characteristics.Objective: The objective of this study was to compare two traditionally used and two novel tableting excipients with regard to their physical and tableting properties as well as their magnesium stearate sensitivity. Avicel® PH102 (microcrystalline cellulose) was compared to the novel co-processed excipient Prosolv® SMCC90 (silicified microcrystalline cellulose), whereas Anhydrous Emcompress® (anhydrous dicalcium phosphate) was compared to the novel spherically granulated excipient Fujicalin® (anhydrous dicalcium phosphate).Materials and methods: True density, particle size, specific surface area (SSA), flowability, tabletability, and magnesium stearate sensitivity of the excipients was determined.Results and discussion: Due to the silification process (Prosolv®) and the unique manufacturing process (Fujicalin®), the novel excipients showed a comparably larger SSA. Hardest tablets by far could be obtained with Prosolv®, followed by Avicel® and Fujicalin®. Avicel® and Prosolv® were sensitive to magnesium stearate, whereas Fujicalin® and Emcompress® did not show lubricant sensitivity. This confirms the plastic deformation behavior of microcrystalline cellulose and the brittle fracture of anhydrous dicalcium phosphate.Conclusion: Compared to the traditional excipients the investigated novel tableting excipients were advantageous with regard to their SSA and their tableting properties.