Pembuatan Selulosa Mikrokristal pada Serat Daun Tigarun (Crateva magna DC.)

Objective: This study aimed to synthesize and characterize Microcrystalline Cellulose (MCC) from ketapang leaves (Terminalia catappa L.) and compare it with commercial Avicel PH 102. Methods: Ketapang leaves underwent delignification using sodium hydroxide (NaOH), followed by acid hydrolysis using optimized Hydrochloric Acid (HCl) concentrations. The resulting Microcrystalline Cellulose (MCC) was characterized through color reaction; organoleptic, solubility, pH, melting point, microscopic, and fourier transform infrared spectroscopy analyses, with Avicel PH 102 as the comparator. Results: The α-cellulose yield from ketapang leaves was 24.13%, and Microcrystalline Cellulose (MCC) yield reached 83.70%. Hydrochloric Acid (HCl) 1 M gave the highest Microcrystalline Cellulose (MCC) yield of 96%. Microcrystalline Cellulose Ketapang Leaves (MCCKL) was a yellowish-white, odorless, tasteless crystalline powder, similar to Avicel PH 102. It was insoluble in water, alcohol, ether, and acids/bases, meeting Microcrystalline Cellulose (MCC) standards. The pH was 6.47 (standard: 5.0–7.5), and the melting point was 262 °C, comparable to Avicel PH 102. Microscopically, Microcrystalline Cellulose Ketapang Leaves (MCCKL) fibers appeared longer and larger but remained suitable as tablet excipients. Fourier Transform Infrared (FTIR) spectroscopy confirmed the presence of O-H, C-H, C-OH, and β-glycoside groups, indicating structural similarity to commercial Microcrystalline Cellulose (MCC). Conclusion: This study demonstrates the successful synthesis of Microcrystalline Cellulose (MCC) from ketapang leaves with an 83.70% yield from 24.13% α-cellulose. The resulting Microcrystalline Cellulose Ketapang Leaves (MCCKL) showed comparable physicochemical properties to commercial Microcrystalline Cellulose (MCC) (Avicel PH 102), including pH, solubility, melting point, and functional groups. Additional tests showed favorable values for flow rate, moisture content, and compressibility, suggesting that Microcrystalline Cellulose Ketapang Leaves (MCCKL) has strong potential as a direct compression tablet filler.

This study is aimed at evaluating the binding effect of Acacia etbaica gum in granule and tablet formulations using paracetamol as a model drug. Some physicochemical properties of the purified gum such as pH, the presence of tannin and dextrin, solubility, viscosity, loss on drying, total ash value, water solubility index, swelling power, moisture sorption, and powder flow properties were investigated. Paracetamol granules were prepared using wet granulation method at 2%, 4%, 6%, and 8% w/w of the Acacia etbaica gum and compared with granules prepared with reference binders (PVP K-30 and Acacia BP) in similar concentrations. The granules were characterized for bulk and tapped densities, compressibility index and Hausner ratio, angle of repose, flow rate, and friability. Finally, the prepared granules were compressed into tablets and evaluated for different tablet characteristics: weight uniformity, thickness, diameter, crushing strength, tensile strength, friability, disintegration time, and in vitro release profile. The physicochemical characterization revealed that tannins and dextrin are absent in the gum, and the gum has acidic pH. Both the moisture content and total ash values were within the official limits. Furthermore, the gum was found to be soluble in cold and hot water but insoluble in organic solvent and exhibited a shear thickening viscosity profile and excellent flow properties with excellent compressibility. The granules prepared with the gum of Acacia etbaica and reference binders showed good particle size distribution and excellent flow and compressibility properties. All the prepared tablets passed pharmacopeial specifications with respect to their uniformity of weight, thickness, and disintegration time. Tablets formulated with Acacia etbaica gum and acacia BP meet the compendial specification for friability at binder concentrations more than 2%. Drug release properties of all the batches formulated with Acacia etbaica, PVP, and acacia BP complied with the pharmacopeial specification. It can be concluded that the gum of Acacia etbaica could be explored as an alternative excipient for its binder effect in granule and tablet formulations.

Background: Suitable α-cellulose and microcrystalline cellulose powders for use in the pharmaceutical industry can be derived from agricultural wastes. Aims: The pharmacopoeial and physicochemical properties of cornstalk α-cellulose (CCC) and cornstalk microcrystalline cellulose powders (MCCC) were compared to a commercial brand of microcrystalline cellulose (Avicel PH101) to evaluate their usefulness as pharmaceutical excipients. Settings and Design: Physicochemical properties of an excipient play a very crucial role in the functions of the excipient; hence, these properties were evaluated and compared with a commercial brand. Materials and Methods: α-cellulose was extracted from cornstalks. Modification of this α-cellulose powder was carried out by its partial hydrolysis with hydrochloric acid (HCl) to obtain a microcrystalline cellulose powder. Their pharmacopoeial, physicochemical and microbiological properties were evaluated using standard methods. Statistical Analysis: OriginPro 8 SR2 v. 0891 (B891) software (OriginLab Corporation USA) was used for statistical evaluation. One-way analysis of variance was used to differentiate between samples and decide where significant differences were established. Results: The yield of α–cellulose from the cornstalks was 32.5%w/w and that of microcrystalline cellulose 26%w/w. All the cellulose samples met all the pharmacopoeial parameters that were carried out. The comparison of physicochemical properties of the CCC, MCCC and Avicel PH101 suggests that the microcrystalline celluloses might have better flow and compression properties than the CCC sample. The three cellulose powders were of high microbial excipient quality. For almost all parameters evaluated, it was generally observed that the MCCC has similar characteristics to Avicel PH101. Conclusions: MCCC can be a suitable alternative to the expensive Avicel PH101as pharmaceutical excipients. Key words: Cornstalk, microcrystalline cellulose, pharmacopoeial properties, physicochemical properties, α-cellulose

Novel multifunctional pharmaceutical excipients derived from microcrystalline cellulose–starch microparticulate composites prepared by compatibilized reactive polymer blending

The most affordable type of tablet is the immediately compressible tablet, which uses microcrystalline cellulose (MCC), a popular pharmaceutical excipient, as a filler or binder. To make it compatible with different active drugs and excipients, we tried to change some physical properties of the MCC. In the current study, we used a chelating agent to pretreat the waste cotton before pulping, bleaching, and finally, hydrochloric acid degradation with a concentration of 2N at 100 °C temperature for 20 min to prepare MCC. The prepared MCC was treated with different concentrations of sodium hydroxide at room temperature or at -20 °C followed by precipitation with hydrochloric acid or ethanol with complete washing with distilled water till neutralization. Evaluation of the degree of polymerization (DP) and FT-IR spectrum confirm the identity of the microcrystalline cellulose. The DP was found to be 216. The bulk density of the unmodified MCC was 0.21 while that of modified MCC varied from 0.253 to 0.594. The modified MCC powder showed good flow properties compared to the unmodified MCC as evaluated by the Hausner index, Carr's index and the angle of repose. The scanning electron microscopy (SEM) of the MCC revealed that the rod shape has been changed to an oval shape due to treatment with sodium hydroxide at -20 °C. The X-ray crystallographic (XRD) analysis indicated that the unmodified MCC and standard MCC showed the crystallinity index (CrI) value of 86.82% and 87.63%, respectively, while the value ranges from 80.18% to 60.7% among the modified MCC powder. The differences in properties of the MCC might be due to the variation of rearrangement of the cellulose chain among the MCC particles due to treatment with different concentrations of a base at different temperatures and precipitation environments. This has enabled us to prepare MCC with different properties which might be compatible with different drugs.

Variability in raw materials presents a challenge for pharmaceutical companies. The varying physicochemical properties can critically influence drug release and bioavailability of the final dosage form. Therefore, a strategy to control this variability is required. In this study the well-established antiepileptic drug carbamazepine (CBZ) was selected as the model drug as it presents one example where variability in raw materials has been linked to bioinequivalence and clinical failures. CBZ shows poor solubility, low potency, and a narrow therapeutic index. Furthermore, CBZ exhibits at least four polymorphic forms and it transforms into the less soluble CBZ dihydrate in water. The purpose of this work was to study the impact of variability in CBZ samples of four different suppliers on the drug release and to suggest a strategy to deal with the sample variability. Thus, the CBZ samples were characterized at preformulation as well as at a formulation level. Polymorphism and morphology of CBZ samples were analyzed by differential scanning calorimetry, X-ray powder diffraction, sieve analysis, and scanning electron microscopy. CBZ samples were characterized by a unidirectional dissolution method measuring disc intrinsic dissolution rate (DIDR) of CBZ raw material and initial drug release in presence of the tablet fillers microcrystalline cellulose (MCC) and mannitol (30–90% drug load). Furthermore, CBZ samples were recrystallized in 1% polyvinylpyrrolidone ethanol solutions as an approach to reduce the sample variability. At the formulation level, a high-dose CBZ tablet was developed with the aim of a tablet formulation that is robust towards the variability in CBZ samples and that conforms to the USP requirements of CBZ tablets for immediate release. Therefore, the superdisintegrant crospovidone (CrosPVP) and the dry binder hydroxypropyl cellulose (HPC) were used, as both are reported to inhibit transformation to CBZ dihydrate. The tablet filler was MCC. All CBZ samples were of p-monoclinic form but differed in their polymorphic purity, particle size, morphology, and intrinsic dissolution rate. The DIDR profiles showed high variability among the CBZ samples. Two inflection points could characterize individual transformation behavior of anhydrous CBZ to CBZ dihydrate. Presence of MCC reduced drug release variability. Recrystallizing CBZ resulted in strongly reduced variability in dissolution and tablet strength and the transformation to CBZ dihydrate was inhibited. However, particle size and morphology could not be controlled and drug release from binary mixtures with MCC presented deviation for one of the recrystallized CBZ samples. For the tablet formulation the optimal condition was with 6% HPC and 5% CrosPVP, where tablet properties of all CBZ samples were at least 70 N tablet hardness, less than 1 min disintegration, and within the USP requirements for drug release. Nonetheless, dissolution curves of the various CBZ samples differed. Excluding the additive sodium laurylsulfate required by the USP monograph and analyzing the optimized tablet formulation in water only, the dissolution curves of the various CBZ samples could not be distinguished anymore (ANOVA, p > 0.05). The impact of variability in CBZ raw materials on the drug release could be characterized by an individual transformation behavior to the CBZ dihydrate. The applied unidirectional dissolution method can be suggested as a straightforward monitoring tool in preformulation studies conforming to the basic tenet of quality by design of FDA’s PAT initiative. To allow a certain variability in CBZ raw materials, it is suggested to incorporate the excipients CrosPVP, HPC, and MCC into the design of a CBZ tablet formulation. The strategy proposed of how to control the variability in CBZ samples includes the monitoring at preformulation level combined with the design of a robust tablet formulation.

In this work, microcrystalline cellulose (MCC) and nanocrystalline cellulose (NCC) was synthesized from cotton linter collected from a textile mill in Bangladesh. The synthesis was carried out through several steps; alkali treatment, NaClO2 bleaching and acid hydrolysis. The acid hydrolysis was conducted with 9N and 12N sulphuric acid (H2SO4) for synthesis of MCC and NCC, respectively. The raw and synthesized samples were characterized by measuring bulk density, FTIR, SEM and WAXD techniques. The bulk density of MCC and NCC is higher than that of the raw sample, due to shorter chain length, diameter and reduction of amorphous region of cellulose chain. The oxidation reaction took place during the MCC and NCC preparation was detected by FTIR spectra. From the SEM images, it is seen that the surface of untreated sample looks relatively smooth as compared to the rough surface of treated samples due to voids formation and absence of wax on the surface. The crystallinity index of MCC and NCC was measured from the peaks at 14.6° and 22.6° (2 angles) of WAXD curves. It shows the enrichment in the proportion of crystalline cellulose in MCC. The thermal stability of the MCC is better than that of other experimented samples. Finally, the synthesized MCC and NCC may be emerging and promising materials with exceptional properties.

Microcrystalline cellulose (MCC) is a bio-based material obtained from purified and partially depolymerized cellulose. The need for cheaper sources of MCC has led to the exploration of other lignocellulosic material based on agricultural residues. Hence, in this study, olive stones were chosen as olive industry produces 37,500 tons of olive-stone waste every year. Microcrystalline cellulose was prepared by acid hydrolysis using hydrochloric or sulfuric acids then bleached. Characterization of the prepared MCC was carried out using attenuated reflectance Fourier transform infrared (ATR-FTIR) spectroscopy and thermal gravimetric analysis (TGA). The crystal structure was studied using XRD. The surfaces of prepared samples were investigated by field emission scanning electron microscope (SEM). In addition, surface area and pore size, as well as particle size distribution of the prepared samples, were measured using nitrogen absorption isotherm and dynamic laser light scattering, respectively. The particle size of samples prepared with sulfuric acid was smaller and therefore the surface area was higher than in case of samples prepared using hydrochloric acid. However, the hydrochloric acid prepared MCC had higher thermal stability than the other sample prepared using sulfuric acid. The properties of prepared MCCs were compared to the commercially available MCC (Avicell PH 101); the results showed good agreement in most properties between olive stone MCC and the commercial one.

Introduction: Microcrystalline cellulose (MCC) is an excipient used in food, cosmetics and pharmaceutical industries especially in the manufacture of tablet. Dendrocalamus asper (betung bamboo) contains high cellulose content at approximately 44.94% and it has potential as raw material of microcrystalline cellulose. Objective: The purpose of this study was to obtain microcrystalline cellulose powder from betung bamboo and it’s physicochemical properties. Methods: The steps to produce microcrystalline cellulose were extraction with n-Hexane: Ethanol (2:1), isolation of alpha cellulose, and acid hydrolysis of alpha cellulose to MCC. The purity of microcrystalline cellulose obtained was identified by infrared spectrophotometry and melting point determination. Other characteristics such as x-ray diffraction, particle size distribution, pH, ash content, moisture content, loss on drying, flow rate, density, scanning electron microscope, and angle of repose were also determined and compared to Avicel PH 101. Results: The Infra-red spectrum obtained were similar to reference Avicel PH 101. The powder was moderately fine, odorless, tasteless and less white compared to reference, particle size distribution 1117.4 nm, pH 6.88, ash contents ± 0.0584%, moisture content 36%, loss on drying 4.59%. Density, flow rate and angle of repose fulfilled the requirements based on the literature. Conclusion: There is a similarity characteristic of MCC obtained and reference. So, there is a possibility for its use as excipient in the future by doing the application studies in food and pharmacy. Key words: Acid hydrolysis, Bamboo betung, Cellulose, Characterization, Microcrystalline cellulose.

Background: Microcrystalline cellulose (MCC) is a popular dry binder in tablet formulation. Differences in its processing methods can significantly affect its tableting properties. Aim: Assessment of the tableting and in-vitro release properties of diazepam tablets formulated with Gossypiumherbaceum (GH) derived MCC that was dried by two different methods. Methods: G.herbaceum bolls were de-lignified in sodium hydroxide solutions to obtain α-cellulose which was hydrolyzed with 2.0 N hydrochloric acid to obtain MCC. The neutralized damp MCC was separated into two portions. One portion was fluid bed dried (MCC-GossF) while the other portion was lyophilized (MCC-GossL). Diazepam tablets were prepared with 20, 30 and 40%w/w of MCC-GossF and MCC-GossL..Avicel PH 102 (AVH-102) served as comparing standard. The formulations were evaluated using standard methods. Results: The powders flowed well and the tablets met with British Pharmacopoiea specifications. Diazepam tablets containing MCC-GossL (DGL) were stronger than those of MCC-GossF (DCF) (p<0.05). The disintegration times were < 2 min and friability ≤ 1%. The strength of tablets containing AVH-102 (DAV) compared well with those of DGL tablets. More than 80% of diazepam was released from the tablets. Conclusion: The GH MCCs served as good dry binders in the formulation of diazepam tablets.

A lack of strategies for the utilization of harvest residues (HRs) has led to serious environmental problems due to an accumulation of these residues or their burning in the field. In this study, wheat and corn HRs were used as feedstock for the production of microcrystalline cellulose (MCC) by treatment with 2-8% sodium hydroxide, 10% hydrogen peroxide and further hydrolysis with 1-2 M hydrochloric acid. The changes in the FT-IR spectra and PXRD diffractograms after chemical treatment confirmed the removal of most of the lignin, hemicellulose and amorphous fraction of cellulose. A higher degree of crystallinity was observed for MCC obtained from corn HRs, which was attributed to a more efficient removal of lignin and hemicellulose by a higher sodium hydroxide concentration, which facilitates the dissolution of amorphous cellulose during acid hydrolysis. MCC obtained from HRs exhibited lower bulk density and poorer flow properties but similar or better tableting properties compared to commercial MCC (CeolusTM PH101). The lower ejection and detachment stress suggests that MCC isolated from HRs requires less lubricant compared to commercial MCC. This study showed that MCC isolated from wheat and corn HRs exhibits comparable tableting behaviour like commercial sample, further supporting this type of agricultural waste utilization.

Characterisation of microcrystalline cellulose derived from wheat bran and evaluation of its ice recrystallisation inhibiting activity.

Brewer’s spent grain (BSG) is the main insoluble solid by-product of the brewing industry. To add value to this non-wood material, microcrystalline cellulose (MCC) was prepared from BSG by alkaline pretreatment, bleaching, and subsequent acid hydrolysis to produce non-wood MCC. This study aimed to optimize MCC production using a statistical design (Box-Behnken) with three factors at three levels: acid concentration (0.5–1.5 M), hydrolysis time (70–90 min) and hydrolysis temperature (55–65 °C), to achieve the maximum yield and crystallinity of MCC derived from BSG. Results from 17 experimental runs revealed that the hydrolysis condition of 0.63 M HCl for 70 min at 61 °C yielded the highest output of 15% with a crystallinity index of 60%. The chemical structures and characteristics of MCC derived from BSG were verified by Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction analysis (XRD). FT-IR analysis showed that the major wavenumbers of lignin and hemicellulose after the chemical processes (1500 cm–1 and 1735 cm–1) decreased by 21.40% and 4.60%, respectively. The XRD chromatogram revealed that the XRD characteristic peaks were sharper after the chemical treatments, indicating an increase in cellulose crystallinity due to removing lignin and hemicellulose. The crystallinity index of MCC derived from BSG ranged from 55–64%, which is comparable in quality to commercial pharmaceutical MCC, Avicel® PH-101 (67.37%). These results demonstrated that MCC from BSG was successfully prepared by acid hydrolysis under optimized conditions. BSG proved a viable non-wood source for preparing MCC for application in the pharmaceutical and nutraceutical industries.

The microcrystalline cellulose is an important ingredient in pharmaceutical, food, cosmetic and other industries. In this study, the microcrystalline cellulose, obtained from the stalk of Sorghum caudatum was evaluated for its physical and tableting characteristics with a view to assessing its usefulness in pharmaceutical tableting. The microcrystalline cellulose, obtained from the stalk of Sorghum caudatum, obtained by sodium hydroxide delignification followed by sodium hypochlorite bleaching and acid hydrolysis was examined for its physicochemical and tableting properties in comparison with those of the well-known commercial microcrystalline cellulose grade, Avicel PH 101. The extraction yield of this microcrystalline cellulose, obtained from the stalk of Sorghum caudatum was approximately 19%. The cellulose material was composed of irregularly shaped fibrous cellulose particles and had a moisture content of 6.2% and total ash of 0.28%. The true density was 1.46. The flow indices showed that the microcrystalline cellulose, obtained from the stalk of Sorghum caudatum flowed poorly. The hydration, swelling and moisture sorption capacities were 3.9, 85 and 24%, respectively. Tablets resulting from these cellulose materials were found to be without surface defects, sufficiently hard and having disintegration time within 15 min. The study revealed that the microcrystalline cellulose, obtained from the stalk of Sorghum caudatum compares favourably with Avicel PH 101 and conformed to official requirement specified in the British Pharmacopoeia 1993 for microcrystalline cellulose.

Microcrystalline cellulose (MCC) is pure partially depolymerized cellulose synthesized from α-cellulose precursor. The MCC can be synthesized by different processes such as reactive extrusion, enzyme mediated, steam explosion and acid hydrolysis. The later process can be done using mineral acids such as H2SO4, HCl and HBr as well as ionic liquids. The role of these reagents is to destroy the amorphous regions remaining the crystalline domains. The MCC is a valuable additive in pharmaceutical, food, cosmetic and other industries. The MCC is one of the most important tableting excipients due to its outstanding dry binding properties of tablets for direct compression. Different properties of MCC are measured to qualify its suitability for such utilization, namely particle size, density, compressibility index, angle of repose, powder porosity, hydration swelling capacity, moisture sorption capacity, moisture content, crystallinity index, crystallite size and mechanical properties such as hardness and tensile strength. Thermogravimetric analysis (TGA) and differential thermal analysis (DTA) or differential scanning calorimetry (DSC) are also important to predict the thermal behavior of the MCC upon heat stresses. The degree of polymerization (DP) of the MCC is typically less than 400, while that for nanocrystalline cellulose is more than 400 extending to several thousands of (1→4)-β-d-glucopyranose units. The MCC particles with size lower than 5µm must not be more than 10% of the total particles. There are several types of the MCC, namely PHs 101, 102, 103, 105, 112, 113, 200, 301 and 302 based on the particle size and subsequent utilization.