Excipient In Tablet Formulations Research Articles

Preparation and evaluation of dual modified Godare (<i> Colocasia esculenta</i>) starch as a sustained release excipient in tablet formulations

Starch obtained from Colocasia esculenta, Araceae (locally known as godare) has been pregelatinized, cross-linked and evaluated as a sustained release excipient and hydrophilic matrix former in tablet formulations. The pregelatinized starch (PGS) was cross-linked in a microwave oven at three different powers (90, 220 and 350 W) and reaction times ranging from 1 to 6 min, using sodium hexametaphosphate (SHMP) as cross-linking agent. Theophylline tablets containing 30, 40, and 50% and the modified starches were compressed at a constant compression force. Dissolution profiles of theophylline were determined in 0.1 N HCl for the first 2 h and then in phosphate buffer pH 6.8 for the remaining 10 h. Degree of cross-linking (DC) increased with increasing reaction power and time. The resulting modified starches were found to be freely flowing, moisture and acid resistant. Two of the nine theophylline tablet formulations sustained the release over the study period of 12 h releasing about 90% of the drug. The in vitro drug release showed best fit to Higuchi and Hixson-Crowell models depending on the polymer-drug ratio and the type of matrix formers. The dual modified starch in a concentration ranging from 40 to 50% exhibited the attributes of sustained release matrix-forming polymer in the tablet formulations studied. Keywords: godare starch, dual modification, microwave, sustained release, hydrophilic matrix

Development of Coprocessed Chitin-Calcium Carbonate as Multifunctional Tablet Excipient for Direct Compression

Owing to the increasing interest in multifunctional excipients for tableting, coprocessing of individual excipients is regularly used to produce excipients of improved multifunctionality superior to individual excipients or their physical mix. The use of chitin as an excipient in tablet formulation is limited because of certain drawbacks such as poor flowability and low true density. The objective of this work is to improve these properties through coprocessing of chitin with calcium carbonate (CaCO3) by precipitating CaCO3 on chitin particles using different methods. In addition, optimization of the coprocessed chitin was carried out to improve the excipient's properties. Physicochemical (CaCO3 content, true density, X-ray diffraction, infrared spectroscopy, and scanning electron microscopy) and functional testing (swelling force, flowability, tensile strength, deformation mechanism, and disintegration time) were used to characterize the coprocessed product. Results showed that the calcite CaCO3 polymorph is precipitated on the chitin surface and that it interacts with chitin at carbonyl- and amide-group level. In addition, the coprocessed excipient has an improved true density and powder flowability, with CaCO3 forming single layer on the chitin particles surface. Tableting studies showed that the coprocessed powder exhibited an intermediate deformation behavior between CaCO3 (most brittle) and chitin (most plastic). Tablets showed acceptable tensile strength and rapid disintegration (2-4 s). These results show the potential use of coprocessed chitin-CaCO3 as a multifunctional excipient for fast disintegration of tablets produced by direct compression.

STUDIES ON MICROCRYSTALLINE CELLULOSE OBTAINED FROM SACCHARUM OFFICINARUM 2: FLOW AND COMPACTION PROPERTIES

Microcrystalline cellulose (MCC) derived from Saccharum officinarum stem was evaluated for its powder flow and compaction properties in order to assess its suitability as a potential direct compression excipient in tablet formulations.  Alpha (I±) cellulose obtained from different sodium hydroxide and bleaching treatments of dried shred S. officinarum stem pulp were hydrolyzed with 2.5 N Hydrochloric acid (2.5 N HCl) to obtain MCC which was coded MCC-Sacc. This was compared with a commercial brand, Avicel PH 102. Results of some powder flow parameters were: Bulk and tapped density (0.41 ± 0.01 and 0.54 ± 0.01 g/mL) respectively, particle density (1.82 ± 0.10), porosity (81.69 ± 0.20), Carr’s index (31.47 ± 0.75 %), Hausner’s quotient (1.47), angle of repose (31.00 ± 1.00 °) and these indices indicate poor flowability. Kawakita model assessment of powder showed good densification and cohesiveness. Compacts of MCC-Sacc showed good uniformity of weight, friability, disintegration and mechanical strength. The Heckel model showed good plasticity and slippage of the material. Values obtained were comparable to Avicel PH 102 in terms of compressibility and mechanical strength, hence MCC-Sacc has a good potential for use as a pharmaceutical excipient in direct compression formulation procedure. Keywords: Microcrystalline cellulose, Saccharum officinarum, Avicel PH 102, powder, compaction.

Chitin’s Functionality as a Novel Disintegrant: Benchmarking Against Commonly Used Disintegrants in Different Physicochemical Environments

Disintegrants are used as excipients to ensure rapid disintegration of pharmaceutical tablets and further ensure proper dissolution of the active pharmaceutical ingredient. This study investigates disintegration mechanisms of chitin and common disintegrants. Swelling assessment (swelling force and swelling ratio) in different media, and compaction behavior (pure or mixed with other excipients) tabletability, deformation (Heckel modeling), and compact disintegration times were investigated on the tested disintegrants (alginic acid calcium salt, crospovidone, sodium starch glycolate, croscarmellose sodium, and chitin). Results show that the physicochemical properties of the disintegration medium such as pH and ionic strength, as well as other formulation ingredients, affect the disintegrant functionalities. Heckel analysis using the mean yield pressure “Py” shows that alginic acid calcium salt is the most brittle among the studied disintegrants, while crospovidone has the most plastic deformation mechanism, followed by chitin. Chitin showed good tabletability and disintegration properties that were not influenced by the physicochemical formulation environment. Chitin is largely available and easily modifiable and thus a promising material that could be used as a multifunctional excipient in tablet formulation.

Modified Starch and its Potentials as Excipient in Pharmaceutical Formulations

Despite its vast commercial value, native starch has some inherent weaknesses when it comes to pharmaceutical application, to mention few include; poor compressibility, low flow ability values and often drug/excipient compatibility problems. In this review, some potentials of modified starch with particular emphasis on their improved functionalities and applicability in pharmaceutical formulations were discussed. Basic requirements for pharmaceutical excipients and various modification methods for starch i.e chemical modification, physical and biotechnological methods were highlighted.Pharmaceutical applications of modified starches as tablet super disintegrant, sustained/ controlled release polymer, plasma volume expanders and as directly compressible excipient in tablet formulations have been cited.

Comparison of microcrystalline characterization results from oil palm midrib alpha cellulose using different delignization method

Oil palm midrib is one of the waste generated by palm plants containing 34.89% cellulose. Cellulose has the potential to produce microcrystalline cellulose can be used as an excipient in tablet formulations by direct compression. Microcrystalline cellulose is the result of a controlled hydrolysis of alpha cellulose, so the alpha cellulose extraction process of oil palm midrib greatly affect the quality of the resulting microcrystalline cellulose. The purpose of this study was to compare the microcrystalline cellulose produced from alpha cellulose extracted from oil palm midrib by two different methods. Fisrt delignization method uses sodium hydroxide. Second method uses a mixture of nitric acid and sodium nitrite, and continued with sodium hydroxide and sodium sulfite. Microcrystalline cellulose obtained by both method was characterized separately, including organoleptic test, color reagents test, dissolution test, pH test and determination of functional groups by FTIR. The results was compared with microcrystalline cellulose which has been available on the market. The characterization results showed that microcrystalline cellulose obtained by first method has the most similar characteristics to the microcrystalline cellulose available in the market.

New multifunctional pharmaceutical excipient in tablet formulation based on citric acid-cyclodextrin polymer

A β-cyclodextrin (β-CD) polymer obtained by crosslinking β-CD with citric acid in its water-insoluble (PCD-I) and soluble (PCD-S) forms was used as a multifunctional direct compression excipient for tablet designing. PCD-I powder was obtained after grinding the solid fraction through a 200μm grid. PCD-S powder was recovered after lyophilization or spray drying of the PCD-S aqueous solutions, eventually followed by a wet granulation step. Both PCD-I and PCD-S powders were characterized, separately and mixed in variable ratios, based on dynamic water vapor sorption, SEM, particle size distribution, tapped density, compressibility, and flowability. PCD-I and spray dried and lyophilized/wet granulated PCD-S, as well as the mixture PCD-I/PCD-S=90/10, presented optimal free flowing characteristics. Then, PCD-I or PCD-S powders - separately or mixed in variable ratios - were used for tablets preparation by direct compression without adding any other excipient (e.g. binder, lubricant, disintegrant etc). As PCD-I decreased, tablets resistance to crushing and disintegration time increased from 15s to 15min (against 30min for β-CD), showing the improved disintegrant functionality of PCD-I, that rapidly swelled once in contact with water. Finally, PCD was force-fed to Sprague-Dawley rats (2g/kg) which were then observed during 14days for any clinical signs of toxicity.

Effect of carboxymethylation on physicochemical, micromeritics and release characteristics of Kyllinga nemoralis starch

Lesser usages of native starch has attracted attention in the modification of starch to incorporate its benefits for pharmaceutical application. A work has been carried out to study the influence of carboxymethylation on the morphological, physico-chemical, powder, spectroscopical and drug discharge characteristics of native starch. Various amount of monochloroacetic acid was used to study the influence of degree of substitution (DS) on the diverse characteristics of modified starch. Amylose content was found to be reduced with the increase in degree of substitution. An enhanced degree of structure deformation was observed with the increment in the DS by the help of scanning electron micrographs. The FT-IR spectra established the polysaccharide nature and the carboxymethylation of the chemically modified starch molecules through the new bands at 1602cm−1, and 1418.69cm−1. The stability of carboxymethyl starches pertaining to the temperature has been revealed by thermogravimetric analysis. Micromeritics of carboxymethylated starches shows their effectiveness as excipients in tablet formulation. The delayed % release of the drug, with the rise in degree of substitution from the tablets prepared marks that the carboxymethyl derivatives of Kyllinga nemoralis rhizomes starch may be used as a suitable source of excipient for sustained release formulations.

PHYSICOCHEMICAL CHARACTERIZATION OF ACID MODIFIED DIOSCOREA STARCH AND ITS EVALUATION AS DIRECTLY COMPRESSIBLE EXCIPIENT IN TABLET FORMULATION

D. abyssinica was partially hydrolyzed in 6% HCl solution at room temperature for different lengths of time, (2, 4, 8, 16, and 32 days), dried using oven- and spray- drying techniques and subsequently investigated as directly compressible excipient in paracetamol tablet formulations. Native dioscorea starch (NDS) and oven dried acid modified dioscorea starch (AMDS) exhibited poor flow characteristics, whereas spray dried AMDS was found to be free flowing powder with 21.37 ± 1.39° angle of repose and 13.24 ± 0.76 g/sec flow rate. Both swelling power and percent solubility of the starches were found to increase with increase in temperature; AMDS showed higher percent solubility of 68.53%. Lubricant sensitivity and dilution potential of spray dried NDS and spray dried AMDS were investigated by incorporating magnesium stearate and paracetamol, respectively. In tablet formulations, spray dried AMDS and Starch 1500® tablets were produced with acceptable tablet characteristics up to 1% and 0.5% magnesium stearate concentrations, respectively. The spray dried AMDS was able to accommodate up to 40% paracetamol with acceptable criteria. Thus, it can be concluded that AMDS can be used as an alternative directly compressible excipient in tablet formulations. Keywords: Dioscorea starch, acid modification, spray drying, directly compressible excipient.

Characterization and Utilization of Starches Extracted from Florencia and Waxy Maize Hybrids for Tablet Formulation: Compaction Behaviour and Tablet Properties

The aim of this work is to analyze the particle characteristics, such as shape, roundness and size, of starches extracted from Florencia and waxy maize hybrids. The micromeritics and structural properties of the samples were examined. The evaluation of flow properties, densification and compression behaviour of the powders was carried out. Physical parameters and swelling characteristics of tablets containing Florencia and waxy maize starch were also studied. Starch samples were compared with respect to their applicability as excipients in tablet formulation. The samples exhibited identical structure and similar particle characteristics. Maize starch extracted from the Florencia dent hybrid showed better flowability and compressibility in tableting experiments, which resulted in better mechanical tablet properties. With regard to utilization as a disintegrant, Florencia starch indicated rapid and intensive swelling and proved to act more effectively in the swelling process than waxy maize starch.

The Rheological Modeling and Effect of Temperature on Steady Shear Flow Behavior of Cordia abyssinica Gum

Steady shear rheological properties of Cordia abyssinica gum, as a novel hydrocolloid, were investigated at different temperatures (30-50°C). The apparent viscosity was drastically affected by temperature, and decreased from 234.9 to 7.46 Pa.s. Cordia gum was exhibited pseudoplastic behavior, which being almost Newtonian at 50°C. Different models including Powerlaw, Herschel-Bulkley and Casson were applied to model rheological trait. The Results were shown that the Herschel-Bulkley model has the best fitness with experimental data. Ascending and descending viscometry data were shown a weak thixotropic behavior particularly at low shear rates. By increasing the temperature in both curves, n decreased and k increased. The apparent viscosities of Cordia gum followed an Arrhenius model and the ηo increased and activation energy diminished as shear rate decreased from 330 to 15/s. Low values of the activation energy implied that Cordia gum can maintain its viscosity at higher temperatures more than BSG and Xanthan. It has a high potential for application in food and neutaceutical products as possess yield stress and pseudoplastic behavior, which enables it to use as an emulsifier, stabilizer or excipient in tablet formulations.

The tableting properties of melibiose monohydrate

In this research, the tableting properties of α-melibiose monohydrate were studied. Melibiose is a disaccharide which bears structural resemblance to lactose, because they both consist of galactose and glucose monosaccharide subunits. Compactibility and deformation behavior of two melibiose batches from different suppliers were studied and compared with α-lactose monohydrate and some other typical tableting excipients. Differences in the deformation behavior were determined comparing the shape of the Heckel plots, the yield pressure values and the strain rate sensitivity (SRS) indexes. In addition, the effect of moisture on the tabletability was studied. According to the yield pressures and SRS indexes melibiose was concluded to be fragmenting, even at higher degree than lactose monohydrate. However, the overall deformation behavior of melibiose was found to be similar to that of lactose monohydrate. Increase in moisture content resulted in higher tensile strengths of tablets for both melibiose batches, but it seemed to have more effect on compactibility of the other batch. In conclusion, melibiose has potential to be used as an excipient in tablet formulations.

Validated stability-indicating high performance thin layer chromatographic method for determination of Ivabradine hydrochloride in bulk and marketed formulation: An application to kinetic study

A sensitive, selective, precise and accurate stability-indicating high-performance thin layer chromatographic method for analysis of Ivabradine hydrochloride (IH) an anti anginal agent, both as a bulk drug and in formulations was developed and validated according to ICH guideline. Densitometric analysis of IH was carried out in the absorbance mode at 287nm using ethyl acetate: 0.389M ammonium acetate in methanol (1:5, v/v) as solvent system. This system was found to give compact spots for IH at an Rf value of 0.36±0.01. Moreover, IH was subjected to acid and alkali hydrolysis, oxidation, accelerated humidity/temperature, wet heat treatment, and photo degradation. The drug undergoes degradation under mainly acidic and basic conditions. Also the degraded products were well resolved from the pure drug with significantly different Rf values. Linearity was found to be in the range of 1200–2800ng/band. The LOD and LOQ for IH were 255.86ng/band and 775.33ng/band, respectively. “Bartlett’s test” and “Lack of fit” applied on peak area for linearity, additionally proved validity of the developed method. Good accuracy and precision were obtained as revealed from %RSD value less than 2. Similarly, no interference was observed from common excipients in tablet formulation as well as degradation product, indicating specificity of the method. As the method could effectively separate the drug from its degradation product, it can be employed as a stability-indicating one. Moreover, proposed method was also utilized to investigate the kinetics of acidic degradation process at different temperatures and first order rate constant, half-life, shelf-life and activation energy were calculated.

Application and Characterization of Gum from Bombax buonopozense Calyxes as an Excipient in Tablet Formulation

This study was undertaken to explore gum from Bombax buonopozense calyxes as a binding agent in formulation of immediate release dosage forms using wet granulation method. The granules were characterized to assess the flow and compression properties and when compressed, non-compendial and compendial tests were undertaken to assess the tablet properties for tablets prepared with bombax gum in comparison with those prepared with tragacanth and acacia gums. Granules prepared with bombax exhibited good flow and compressible properties with angle of repose 28.60°, Carr’s compressibility of 21.30% and Hausner’s quotient of 1.27. The tablets were hard, but did not disintegrate after one hour. Furthermore, only 52.5% of paracetamol was released after one hour. The drug release profile followed zero order kinetics. Tablets prepared with bombax gum have the potential to deliver drugs in a controlled manner over a prolonged period at a constant rate.

Wet granulation in laboratory-scale high shear mixers: Effect of chopper presence, design and impeller speed

The effect of the main means of agitation in a high shear mixer has been investigated in this study. Granulation runs have been performed on a fine cohesive microcrystalline cellulose powder (Avicel 105, d 50 = 20 μm) often used as a pharmaceutical excipient in tablet formulations in two bowls of a Mi-Pro® laboratory high shear mixer with a capacity of 0.9 and 1.9 L, respectively. Torque curves recorded during granulation are found to allow good control of the process while increasing impeller speed is found to generally reduce granule size and the onset of breakage seems to occur for similar values of impeller tip speed. As a general rule, the chopper allows for better binder distribution in the Mi-Pro® and is found to be necessary for successful granulation at low to moderate impeller speeds. For high impeller speeds in excess of 4.4 m/s with or without a chopper, similar granule sizes and growth mechanisms are observed. Granule roundness was found to increase with impeller speed up to a certain speed after which granule roundness has been found to decrease with increasing impeller speed most probably because of increased breakage of the granules. Dry granule strength has been found to increase with increasing impeller speed, presenting only a slight decrease at the highest impeller speed studied.

Evaluation of cellulose II powders as a potential multifunctional excipient in tablet formulations

The use of UICEL-A/102 and UICEL-XL, the cellulose II powders, as a multifunctional direct compression excipient in the design of tablets containing hydrochlorothiazide (HCTZ) or ibuprofen (IBU), the model low and high dose drugs, respectively, has been reported. Commercial Oretic ® and Advil ® tablets containing HCTZ and IBU, respectively, and tablets made using Avicel ® PH-102—the most commonly and widely used commercial direct compression excipient, were used in the study for comparison purposes. Tablets were made by first blending drug with the excipient and then with stearic acid, a lubricant, in a V-blender, followed by compressing into a tablet on a hydraulic press using 105 MPa of compression pressure and a dwell time of 30 s. The crushing strengths of HCTZ tablets decreased in the order Avicel ® PH-102 > UICEL-XL, UICEL-A/102 > Oretic ® and of IBU tablets in the order Avicel ® PH-102 ≥ UICEL-XL ⋍ UICEL-A/102 > Advil ®. The friability values for all tablets were well below the maximum 1% USP tolerance limit. UICEL-A/102 and UICEL-XL tablets containing HCTZ disintegrated rapidly (<25 s). Oretic ® tablets disintegrated in about 60 s, while Avicel ® PH-102 tablets remained intact during 1 h test period. The IBU tablets made using UICEL-A/102 disintegrated the fastest, UICEL-XL and Advil ® tablets the next, and Avicel ® PH-102 tablets remained intact. All tablets, except for those of Avicel ® PH-102, conformed to the USP drug release requirements. These results conclusively show that UICEL-A/102 and UICEL-XL have the potential to be used as filler, binder, and disintegrant, all-in-one, in the design of tablets containing either a low dose or high dose drug by the direct compression method.

Multivariate Methods in Developing an Evolutionary Strategy for Tablet Formulation

The aim of this study was to develop a new strategy for choosing excipients in tablet formulation. Multivariate techniques such as principal component analysis (PCA) and experimental design were combined in a multivariate design for screening experiments. Of a total 87 investigated excipients, the initial screening experiments contained 5 lubricants, 9 binders, and 5 disintegrants, and 35 experiments were carried out. Considering a reduced factorial design was used, the resulting PCA and partial least squares (PLS) models offered good insight into the possibilities of tablet formulation. It also offered solutions to the problems and clearly gave directions for optimum formulations. Further, it offered several alternatives for achieving quality formulations. Additional experiments conducted to validate and verify the usefulness of the model were successful, resulting in several tablets of good quality. The conclusion is that a multivariate strategy in tablet formulation is efficient and can be used to reduce the number of experiments drastically. Combining multivariate characterization, physicochemical properties, experimental design, multivariate design, and PLS would lead to an evolutionary strategy for tablet formulation. Since it includes a learning strategy that continuously incorporates data for new compounds and from conducted experiments, this would be an even more powerful tool than expert systems.

Influence of micronization on the compaction properties of an investigational drug using tableting index analysis

Tableting index analysis was used to study the compaction properties of two lots of an investigational drug substance alone and in combination with excipients in tablet formulations. Lot A was pin-milled while lot B was micronized using a fluid energy mill. Light scattering analysis demonstrated a median particle size of 23.4 and 5.0 μm for lots A and B, respectively. Results from tableting index analysis indicated a significantly higher average tensile strength and bonding index for the micronized material at solid fractions of 0.80, 0.85, and 0.90. The enhanced bonding could be attributed to approximately a five-fold increase in particle surface area and associated increase in the true contact areas between the micronized particles. Brittle fracture index testing demonstrated slightly higher brittle propensities for the pure micronized compacts at each solid fraction. Tableting index analysis was also performed on tableting formulations containing milled and micronized drug at both the 30 and 65% level. The formulation containing 65% micronized drug demonstrated a significantly higher bonding index over the equivalent formulation containing milled drug. However, there was minimal difference in the bonding index between the formulations containing 30% micronized and milled drug substance. Results suggested that the incorporation of micronized drug could significantly increase the bonding propensities of high dose formulations in comparison with formulations containing conventionally milled drug substance. In addition, tableting index analysis was shown to be a very useful technique to quantitatively study the effect of micronization on compaction properties of tableting formulations. © 1997 Elsevier Science B.V. All rights reserved

A thermogravimetric study of ascorbic acid and its excipients in pharmaceutical formulations

The thermal decomposition of ascorbic acid and its excipients in tablet formulations was studied under an atmosphere of nitrogen using a thermogravimetric balance. To maximize the tendency of an interaction, binary mixtures (1:1 by weight) of drug and excipient and between excipients were utilized. Two new methods were employed to assess the change in reactivities, and the thermal behavior of the materials under investigation. In the first method, named the α s− α r method, the solid state reactivity of the sample was compared to that of a reference. The term α refers to the extent of the reaction. The second method is called the W p W t method. In this method, the effect of the excipients on the decomposition pattern of ascorbic acid can be shown. The terms W p and W t refer to the percentage of residual solid material obtained experimentally ( W p) and theoretically ( W t). The ratio W p W t is reported at various values of temperature.

A drug dissolution monitor employing multiple fiber optic probes and a UV/visible diode array spectrophotometer.

A traditional dissolution pumping system was recently replaced with a fiber optic interface between the spectrometer and the samples. However, the system was limited to a single sample vessel. In this study, a dissolution testing system with six vessels connected to a diode array spectrometer via six optical fibers was investigated. A bifurcated fiber optic bundle was used to transfer the light from the source to the dissolution vessels and was networked so that spectra of each sample can be measured periodically. A full spectrum calibration method based on Principal Component Regression (PCR) was used to determine the concentrations of active ingredients and to account for interferences due to excipients in tablet formulations. Results on this new fiber optic interface system are compared with those obtained previously with the traditional pumping system. Standard errors of prediction are between 1.5 and 3.2% using cross-validation and between 1.1 and 1.7% for the direct validation of two active ingredients in two different drug formulations.