Pre-formulation studies on moisture absorption in microcrystalline cellulose using differential thermo-gravimetric analysis

A study on the differential thermo-gravimetric (DTG) measurements of microcrystalline cellulose (MCC) containing moisture indicated that particle size affected the amount of bound water and the flow indices. Thermal analysis of 6 commercial grades of MCC powders and MCC/water blends were performed using a thermo-gravimetric analyzer. These MCCs were differentiated by their particle size, bulk and tapped densities, crystallinity and micromeritic properties. From the DTG curves, it was observed that water loss from the MCC/water blends occurred in 3 phases which corresponded to the different states of water associated with the solid particles. Area under the third phase, or the falling rate phase, can be associated with the release of water that was physically shielded or bound to the solid. This water may be referred to as "structured" water. The large particle size grades of MCC-Avicel PH 102, PH 302 and Pharmacel 102 were found to possess smaller quantities of structured water. Water vapor sorption results revealed the monolayer capacities for the respective MCC grades. The amount of structured water appeared to correspond to the existence of bilayers on the surface of the small particle size MCC grades. Using the avalanche flow assessment method, flow properties of small particle size grades of MCC were found to be poorer as indicated by the significant correlation between their flow indices and size, in addition to the longer mean times to avalanche.     

The influence of microcrystalline cellulose grade on shape and shape distributions of pellets produced by extrusion-spheronization.

In this study, five microcrystalline cellulose (MCC) grades were physically characterized and their extrusion-spheronization behaviours were characterized in terms of water requirements and pellet shape profiles. It was found that the MCC grades differed significantly in the physical properties investigated. Physical properties of MCC were found to influence the water requirement for extrusion-spheronization. MCC grades of higher bulk densities, lower porosities and water retentive capacities required less water to produce pellets of equivalent size. These MCC grades were also found to produce pellets of lower sphericity and wider shape distributions. Packing of MCC particles within the agglomerate played a role in determining amount of water retention and pellet rounding during spheronization. However, there was a limit to the influence of packing density on the rate of pellet rounding because poor packing resulted in higher water retentive capacity, which also limited the rate of rounding.     

Compatibility of sildenafil citrate and pharmaceutical excipients by thermal analysis and LC–UV

The evaluation of sildenafil citrate (SC), the best-selling drug for treatment of impotence, for compatibility with various excipients was investigated using thermal and isothermal stress testing. Differential scanning calorimetry (DSC), hot-stage microscopy (HSM) and liquid chromatography (LC) with ultraviolet detection were successfully employed to investigate the compatibility between SC and various excipients commonly used in solid form in the pharmaceutical industry. The studies were performed using 1:1 (m/m) drug/excipient physical mixtures and samples were stored under accelerated stability conditions (40 °C at 75% relative humidity). All excipients tested (such as colloidal silicon dioxide, croscarmellose sodium, lactose, mannitol and sucrose) showed potential incompatibilities by DSC and LC analysis after accelerated stability testing. However, some incompatibilities were not detected by the DSC method and were observed only when LC analysis was performed. HSM was able to differentiate active pharmaceutical ingredient degradation from solubilisation, supporting the interpretation of DSC in excipients where thermal events either overlapped or disappeared. The combination of both the analytical techniques (DSC and LC) and use of a stability chamber is extremely helpful in detecting incompatibilities and providing more robust and accurate approaches for pre-formulation studies.     

Green preparation of porous corncob microcrystalline cellulose,and its properties and applications

Cellulose - Microcrystalline cellulose (MCC), a cellulosic functional material, is widely used in food, pharmaceutical and cosmetics industries. However, conventional methods for MCC preparation...     

Hydrophobic similarity between molecules: a MST-based hydrophobic similarity index

A similarity index based on the hydrophilic/hydrophobic properties of molecules is presented. Such an index is defined based on the fractional partition of the free energy of solvation developed within the framework of the self-consistent reaction field MST model, which divides the free energy of solvation or the free energy of transfer into contributions assigned to the surface elements defining the solute/solvent interface. These surface contributions can be integrated to derive atomic or group contributions. The suitability of the index to compute the molecular similarity based on hydrophobic/hydrophilic properties is examined by considering their application in a variety of test systems, including structure-activity relationships, absorption properties, and molecular recognition. The similarity index is expected to be a very powerful tool in molecular similarity studies for compounds of chemical, biochemical, and pharmaceutical interest.     

Synthesis and characterization of microcrystalline cellulose powder from corn husk fibres using bio-chemical route

In the present study low cost microcrystalline cellulose (MCC) powder was prepared from cornhusk fibres, extracted chemically followed by anaerobic consortium treatment. Cornhusk fibres were treated with 10% alkali at 120 °C for 60 min followed by anaerobic consortium treatment for 3 days. It was then bleached with hydrogen peroxide and finally washed. Bleached pulp was hydrolysed using 4 N HCl to get the MCC. In the present investigation, we have characterized the MCC prepared from cornhusk fibres thoroughly for its physico-chemical properties and compared with Avicel^®-PH 101, a commercial grade MCC. Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), X-Ray Powder Diffraction (XRD) and Differential Scanning Calorimetry (DSC) were used for characterization of samples. Similarly the powder and flow properties of the MCC prepared from cornhusk fibres were also investigated and the results were compared with Avicel^®-PH 101. Our results showed that various properties and the purity of MCC prepared from cornhusk fibres are comparable to the commercial grade MCC. Since, cornhusk is an agricultural waste product, MCC obtained from cornhusk fibres will be from cheaper raw materials than current market MCC.     

Investigation of the compatibility between kaempferol and excipients by thermal,spectroscopic and chemometric methods

Journal of Thermal Analysis and Calorimetry - Compatibility is an important step in pre-formulation studies during the development of solid dosage forms. In the present study, we used thermal...     

Selective hydrolysis of cellulose for the preparation of microcrystalline cellulose by phosphotungstic acid

Microcrystalline cellulose (MCC), prepared from natural cellulose through acid hydrolysis, has been widely used in the food, chemical and pharmaceutical industries because of its high degree of crystallinity, small particle size and other characteristics. Being different from conventional mineral acids, phosphotungstic acid (H₃PW₁₂O₄₀, HPW) was explored for hydrolyzing cellulose selectively for the preparation of MCC in this study. Various reaction parameters, such as the acid concentration, reaction time, temperature and solid-liquid ratio, were optimized. Rod-like MCC was obtained with a high yield of 93.62 % and also exhibited higher crystallinity and narrower particle diameter distribution (76.37 %, 13.77–26.17 μm) compared with the raw material (56.47 %, 32.41–49.74 μm) at 90 °C for 2 h with 58 % (w/w) HPW catalyst and a solid-liquid radio of 1:40. Furthermore, HPW can easily be extracted and recycled with diethyl ether for four runs without affecting the quality of the MCC products. The technology of protecting the crystalline region while selectively hydrolyzing the amorphous region of cellulose as much as possible by using HPW is of great significance. Due to the strong Brønsted acid sites and highest activity in solid heteropoly acid, the use of effective homogeneous HPW may offer an eco-friendly and sustainable way to selectively convert fiber resources into chemicals in the future.     

PaDEL‐DDPredictor: Open‐source software for PD‐PK‐T prediction

ADMET (absorption, distribution, metabolism, excretion, and toxicity)‐related failure of drug candidates is a major issue for the pharmaceutical industry today. Prediction of PD‐PK‐T properties using in silico tools has become very important in pharmaceutical research to reduce cost and enhance efficiency. PaDEL‐DDPredictor is an in silico tool for rapid prediction of PD‐PK‐T properties of compounds from their chemical structures. It is free and open‐source software that, has both graphical user interface and command line interface, can work on all major platforms (Windows, Linux, and MacOS) and supports more than 90 different molecular file formats. The software can be downloaded from http://padel.nus.edu.sg/software/padelddpredictor . © 2012 Wiley Periodicals, Inc.     

A study of the mechanical, thermal and morphological properties of microcrystalline cellulose particles prepared from cotton slivers using different acid concentrations

Microcrystalline cellulose (MCC) particles are mostly prepared by acid hydrolysis of various agro sources. Acid hydrolysis is usually carried out with high concentration (64 wt%) of sulfuric acid. Here, an attempt has been made to optimize lower acid concentrations which can effectively produce MCC particles. In this work, different concentrations of sulfuric acid (20, 30, 35, 40, 47 and 64 wt%) have been used to prepare MCC particles, which have been characterized by XRD, particle size analysis, scanning electron microscopy, transmission electron microscopy, nanoindentation and thermogravimetric analysis. MCC prepared with 35 and 47% sulfuric acid (MCC 35 and MCC 47) had finest particle size and fibrils were produced in the range of 15–25 nm. MCC 20 showed wide particle size distribution, indicating low breakdown of the cellulose chains. The energy absorption behavior and mechanical properties of the MCC pellets were determined by nanoindentation test for the first time. MCC 35 pellets exhibited lowest modulus and hardness.     

MIMA—a software for analyte identification in MCC/IMS chromatograms by mapping accompanying GC/MS measurements

Ion mobility spectrometry coupled to multi capillary columns (MCC/IMS) combines highly sensitive spectrometry with a rapid separation technique. MCC\IMS is widely used for biomedical breath analysis. The identification of molecules in such a complex sample necessitates a reference database. The existing IMS reference databases are still in their infancy and do not allow to actually identify all analytes. With a gas chromatograph coupled to a mass selective detector (GC/MSD) setup in parallel to a MCC/IMS instrumentation we may increase the accuracy of automatic analyte identification. To overcome the time-consuming manual evaluation and comparison of the results of both devices, we developed a software tool MIMA (MS-IMS-Mapper), which can computationally generate analyte layers for MCC/IMS spectra by using the corresponding GC/MSD data. We demonstrate the power of our method by successfully identifying the analytes of a seven-component mixture. In conclusion, the main contribution of MIMA is a fast and easy computational method for assigning analyte names to yet un-assigned signals in MCC/IMS data. We believe that this will greatly impact modern MCC/IMS-based biomarker research by “giving a name” to previously detected disease-specific molecules.     

A Study on the Preparation,Structure, and Properties of Microcrystalline Cellulose

Abstract

The preparation, structure, and properties of microcrystalline cellulose (MCC) from rice straw were investigated by IR, x-ray, viscometry, polarizing microscope, SEM, etc. The results are as follows:

1. The leveling-off degree of polymerization (LODP) obtained from rice straw is about 80–150. The dimensions of MCC granules are 20–30 μm length, 0.5–0.8 μm thick, and the crystallinity is about 80%.

2. The aqueous suspension of a certain concentration of MCC can form a gel under the effect of shear force. The viscosity of MCC gel increased with an increasing content of MCC in water. A sharper increase of viscosity occurred in the 3–6% range.

3. The addition of one or two valence salts into the MCC gel increased the viscosity.

4. The viscosity of MCC gel has its maximum value at pH 8.

5. The MCC gel as an emulsifying agent can form a stable emulsion in the oil/water system when the ratio of oil/water is below 6/4.     

Characterization of Natural Anthocyanin Indicator Based on Cellulose Bio-Composite Film for Monitoring the Freshness of Chicken Tenderloin

Intelligent packaging with indicators that provide information about the quality of food products can inform the consumer regarding food safety and reduce food waste. A solid material for a pH-responsive indicator was developed from hydroxypropyl methylcellulose (HPMC) composited with microcrystalline cellulose (MCC). MCC at 5%, 10%, 20%, and 30% w/w was introduced into the HPMC matrix and the physical, barrier, thermal, and optical properties of the HPMC/MCC bio-composite (HMB) films were analyzed. At 5, 10, and 20% MCC, improved mechanical, transparency, and barrier properties were observed, where HMB with 20% of MCC (H20MB) showed the best performance. Therefore, H20MB was selected as the biodegradable solid material for fabricating Roselle anthocyanins (RA) pH sensing indicators. The performance of the RA-H20MB indicator was evaluated by monitoring its response to ammonia vapor and tracking freshness status of chicken tenderloin. The RA-H20MB showed a clear color change with respect to ammonia exposure and quality change of chicken tenderloin; the color changed from red to magenta, purple and green, respectively. These results indicated that RA-H20MB can be used as a biodegradable pH sensing indicator to determine food quality and freshness.     

Desirability-based methods of multiobjective optimization and ranking for global QSAR studies. Filtering safe and potent drug candidates from combinatorial libraries

Up to now, very few applications of multiobjective optimization (MOOP) techniques to quantitative structure-activity relationship (QSAR) studies have been reported in the literature. However, none of them report the optimization of objectives related directly to the final pharmaceutical profile of a drug. In this paper, a MOOP method based on Derringer's desirability function that allows conducting global QSAR studies, simultaneously considering the potency, bioavailability, and safety of a set of drug candidates, is introduced. The results of the desirability-based MOOP (the levels of the predictor variables concurrently producing the best possible compromise between the properties determining an optimal drug candidate) are used for the implementation of a ranking method that is also based on the application of desirability functions. This method allows ranking drug candidates with unknown pharmaceutical properties from combinatorial libraries according to the degree of similarity with the previously determined optimal candidate. Application of this method will make it possible to filter the most promising drug candidates of a library (the best-ranked candidates), which should have the best pharmaceutical profile (the best compromise between potency, safety and bioavailability). In addition, a validation method of the ranking process, as well as a quantitative measure of the quality of a ranking, the ranking quality index (Psi), is proposed. The usefulness of the desirability-based methods of MOOP and ranking is demonstrated by its application to a library of 95 fluoroquinolones, reporting their gram-negative antibacterial activity and mammalian cell cytotoxicity. Finally, the combined use of the desirability-based methods of MOOP and ranking proposed here seems to be a valuable tool for rational drug discovery and development.     

Influence of cellulose type on the properties of extruded pellets. Part I. Physicochemical characterisation of the cellulose types after homogenisation

 The physicochemical properties of different types of powdered cellulose (PC) and microcrystalline cellulose (MCC) were studied by examining the changes in particle size, viscosity and specific surface area after a homogenisation process. An additional characterisation was carried out using X-ray diffractometry. A preliminary investigation using a type of MCC showed that increasing the homogenisation pressure and the number of passage cycles led to a significant decrease in the particle size and simultaneously to a remarkable increase in the specific surface area and viscosity. Most MCC types showed the same pattern during the homogenisation process. “Colloidal” MCC displayed a higher viscosity than the others but without significant change in the viscosity after different homogenisation cycles. In contrast to this behaviour of the MCCs, the PCs showed no remarkable change in the particle size but did show a marked change in their viscosity. Furthermore, only MCC suspensions, with the exception of “colloidal” MCC, agglomerated after the homogenisation process, whereas this was not seen in the PC suspensions. Hence, since the MCC types as well as the PC types originally had the same chemical structure, this different behaviour among these types can only be attributed to their different physical properties. Received: 27 July 1999/Accepted: 15 December 1999     

Effect of microcrystalline and nanocrystals cellulose fillers in materials based on PLA matrix

The aim of this work was to compare the effects of microcrystalline cellulose (MCC) and cellulose nanocrystals (CNC) addition on the properties of PLA matrix. The CNC were obtained by acid hydrolysis of the MCC. Both MCC and CNC were separately incorporated in PLA at ratios of 3, 5 and 7 wt%. In some compositions, organophilic silica (R972) was added to improve the cellulose-matrix compatibility. The properties of the materials were evaluated by FTIR, XRD, NMR and mechanical tests. Functional groups and crystalline structure of MCC and CNC were determined by FTIR and XRD, respectively. NMR T₁H values showed that films containing CNC presented better interfacial interaction than those containing MCC, and indicated that R972 acts as compatibilizer. MCC and CNC acted as nucleating agents for PLA crystallization and there was an improvement in the mechanical performance of materials with the addition of CNC.     

Spray desorption collection: an alternative to swabbing for pharmaceutical cleaning validation

Spray Desorption Collection (SDC) allows for much larger areas of surfaces to be sampled compared to traditional swabbing techniques, providing a valuable pre-concentration advantage. Closely related to desorption electrospray ionization (DESI), analytes from the sample surface are collected onto a selected collection surface, which in a second step can be analyzed directly. Here we demonstrate the application of SDC as a large surface area sampling tool coupled with paper spray MS (PS-MS) and demonstrate its capabilities for cleaning validation of pharmaceutical equipment for both acidic and basic active ingredients from an aluminium surface.     

A labeled substrate approach to discovery of biocatalytic reactions: a proof of concept transformation with N-methylindole

Biocatalysis has become an important method in the pharmaceutical industry for the incorporation of new functionality in small molecules. Currently this method is limited in the types of reactions that can be carried out and no strategy exists to systematically screen for new biocatalyzed reactions. This study involves the development of a medium throughput screen to identify and optimize new reactions using a series of marine-derived bacterial cell lines, which were screened against several (13)C labeled organic substrates. The reactions were analyzed using (13)C NMR as the primary screening tool. We describe the discovery of a bacterial catalyzed indole oxidation reaction in which complete conversion of (13)C labeled N-methyl indole to 3-hydroxyindole was observed. In addition, the sensitivity of this reaction to dO(2) levels can be exploited to oxidize to either 3-hydroxyindole or 2-oxoindole. This new platform sets up an important tool for the discovery of new organic transformations using an extensive library of marine bacteria.     

Analysis of phase transition and dehydration processes of nevirapine

Solid-state characterization of crystalline drugs is an important pre-formulation step for the development and design of solid dosage forms, such as pellets and tablets. In this study, phase transition and dehydration processes of nevirapine have been studied by differential scanning calorimetry and thermogravimetry differential thermal analysis to overcome the problems of drug formulation, namely poor solubility and poor content uniformity. Phase solubility studies elucidated the mechanism of enhanced nevirapine solubility.     

Sequential one-pot combination of multi-component and multi-catalysis cascade reactions: an emerging technology in organic synthesis

Creating sequential one-pot combinations of multi-component reactions (MCRs) and multi-catalysis cascade (MCC) reactions is a challenging task that has already emerged as a new technology in synthetic organic chemistry. Through one-pot sequential combination of MCRs/MCC reactions, the chemical products (fine chemicals, agrochemicals and pharmaceuticals) that add value to our lives can be produced with less waste and greater economic benefits. Within this Emerging Area, we describe our recent developments and designs for sequential one-pot MCRs/MCC reactions to facilitate their realization as biomimetics in organic chemistry.