Excipients For Solid Dosage Forms Research Articles

Effects of Alkaline Solvent Type and pH on Solid Physical Properties of Carrageenan from Eucheuma cottonii

The effects of alkali type and pH on the physical properties of carrageenan have been extensively studied. However, their effects on certain characteristics of solid-state properties of carrageenan have not been identified. This research aimed to investigate the effect of alkaline solvent type and pH on the solid physical properties of carrageenan isolated from Eucheuma cottonii. Carrageenan was extracted from the algae using NaOH, KOH, and Ca(OH)2 at pHs of 9, 11, and 13. Based on the results of preliminary characterization, including yield, ash content, pH, sulphate content, viscosity, and gel strength, it was found that all samples followed Food and Agriculture Organization (FAO) specifications. The swelling capacity of carrageenan based on the type of alkali was KOH > NaOH > Ca(OH)2. The FTIR spectra of all samples were in agreement with that of standard carrageenan. The molecular weight (MW) of carrageenan using KOH as the alkali followed the order pH 13 > pH 9 > pH 11, while using NaOH, the order was pH 9 > pH 13 > pH 11, and while using Ca(OH)2, the order was pH 13 > pH 9 > pH 11. The results of the solid-state physical characterization of carrageenan with the highest MW in each type of alkali showed that the morphology of carrageenan using Ca(OH)2 has a cubic shape and is more crystal-like. The order of crystallinity of carrageenan using different types of alkali was Ca(OH)2 (14.44%) > NaOH (9.80%) > KOH (7.91%), while the order of density was Ca(OH)2 > KOH > NaOH. The order of solid fraction (SF) of the carrageenan was KOH > Ca(OH)2 > NaOH, while the tensile strength when using KOH was 1.17, when using NaOH it was 0.08, and while using Ca(OH)2, it was 0.05. The bonding index (BI) of carrageenan using KOH = 0.04, NaOH = 0.02, and Ca(OH)2 = 0.02. The brittle fracture index (BFI) of the carrageenan was KOH = 0.67, NaOH = 0.26, and Ca(OH)2 = 0.04. The order of carrageenan solubility in water was NaOH > KOH > Ca(OH)2. These data can be used as the basis for the development of carrageenan for excipients in solid dosage forms.

Impact of Amylose-Amylopectin Ratio of Starches on the Mechanical Strength and Stability of Acetylsalicylic Acid Tablets

The two main components of starch — amylose and amylopectin, are responsible for its interaction with moisture. This study investigated how moisture sorption properties of the starches with different amylose-amylopectin ratio impacted tablet properties including drug stability. The starch samples were equilibrated to 33, 53, and 75% relative humidity (RH) and then assessed for tabletability, compactibility, and yield pressure. Effect of humidity on viscoelastic recovery was also evaluated. Tabletability and compactibility of high-amylose starch were better than that of high-amylopectin starch at 33 and 53% RH. However, at 75% RH, the reverse was observed. In terms of yield pressure, high-amylose starch had lower yield pressure than high-amylopectin starch. High-amylose starch tablets also exhibited lower extent of viscoelastic recovery than high-amylopectin starch tablets. The variations in the tableting properties were found to be related to relative locality of the sorbed moisture. Degradation of acetylsalicylic acid in high-amylose starch tablets at 75% RH, 40°C was less than the tablets with high-amylopectin starch. This observation could be attributed to the greater amount of water molecules binding sites in high-amylose starch. Furthermore, most of the sorbed moisture of high-amylose starch was internally absorbed moisture, therefore limiting the availability of diffusible sorbed moisture for degradation reaction. Findings from this study could provide better insights on the influence of amylose-amylopectin ratio on tableting properties and stability of moisture-sensitive drugs. This is of particular importance as starch is a common excipient in solid dosage forms.

Application of Aquasolv Lignin in ibuprofen-loaded pharmaceutical formulations obtained via direct compression and wet granulation

AS (Aquasolv) Lignin produced via Liquid Hot Water Pretreatment and Enzymatic Hydrolysis has shown potential as an active pharmaceutical ingredient and/or excipient in solid dosage forms. Moreover, lignin is safe to consume and presents antioxidant and antidiabetic capacity, properties that can add to solid dosage forms in pharmaceuticals. This work aimed to evaluate the performance of tablets produced via direct compression and wet granulation when lignin is used in combination with commercial excipients. In order to find optimal tablet performance, different lignin formulations were assessed, and the concentrations were given by extreme vertices mixture design (13 formulations). The blends were composed of AS Lignin, Microcrystalline Cellulose, and Lactose monohydrate and the optimized blend was found to be 14.53 w/w% of disintegrant, 26.57 w/w% of binder and 58.9 w/w% of AS lignin. This proportion was further used to evaluate the performance of lignin-based tablets in drug release, using Ibuprofen as a drug model (50 w/w% and 70 w/w%) and for comparison of direct compression with wet granulation. Direct compressed tablets resulted in higher drug dissolution rates when compared with wet granulation, nevertheless; both tableting techniques showed promising results for lignin. More than 5 formulations tested in this work are compliant with International Pharmacopoeia regulations for solid dosage pharmaceutical forms, thus AS Lignin shows potential to be used as an excipient in pharmaceutical formulations. Industrial relevanceIndustrially, AS Lignin appears as promising excipient in the pharmaceutical technologies as well as boost in the biorefining technologies in the following years. Lignin produced is free of sulfur, can be labelled as clean and environmentally-friendly and in this study, was proven this non-cytotoxic AS lignin can be used for excipients and drug carriers. The findings in this paper showed the use of product formulation for life science purposes, thus stressing one of possibilities for lignin valorization in biorefineries.

Quantitative analysis of solid dosage forms of cefixime using Raman spectroscopy.

Quantification of antibiotics is of significant importance because of their use in the prevention and treatment of different diseases. Cefixime (CEF) is a cephalosporin antibiotic that is used against bacterial infections. In the present study, Raman spectroscopy has been applied for the identification and quantification of Raman spectral features of cefixime with different concentrations of Active Pharmaceutical Ingredient (API) and excipients in solid dosage forms. The changes in Raman spectral features of API and excipients in the solid dosage forms of cefixime were studied and Raman peaks were assigned based on the literature. Multivariate data analysis techniques including the Principal Component Analysis (PCA) and Partial Least Squares Regression analysis (PLSR) have been performed for the qualitative and quantitative analysis of solid dosage forms of cefixime. PCA was found helpful in differentiating all the Raman spectral data associated with the different solid dosage forms of cefixime. The coefficient of determination (R2), mean absolute error (MAE), and mean relative error (MRE) for the calibration data-set were 0.99, 0.72, and 0.01 respectively and for the validation data-set were 0.99, 3.15, and 0.02 respectively, that shows the performance of the model. The root mean square error of calibration (RMSEC) and root mean square error of prediction (RMSEP) were found to be 0.56mg and 3.13mg respectively.

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.

Impact of Metallic Stearates on Disproportionation of Hydrochloride Salts of Weak Bases in Solid-State Formulations.

Excipient-induced salt disproportionation (conversion from salt form to free form) in the solid state during storage or manufacturing is a severe formulation issue that can negatively influence product performance. However, the role of excipient properties on salt disproportionation and mechanisms of proton transfer between salt and excipients are still unclear. Moreover, knowledge about the formation of disproportionation products and the consequent impact of these reactions products on the disproportionation process is still inadequate. In the present study, three commonly used lubricants (sodium stearate, calcium stearate, and magnesium stearate) were mixed with a hydrochloride salt as binary mixtures to examine their different capabilities for inducing salt disproportionation at a stressed storage condition (40 °C/65% RH). The overall objective of this research is to explore factors influencing the kinetics and extent of disproportionation including surface area, alkalinity, hygroscopicity, formation of new species, etc. In addition, we also aim to clarify the reaction mechanism and proton transfer between the model salt and stearates to provide insight into the in situ formed reaction products. We found that the properties of stearates significantly affect the disproportionation process in the initial stage of storage, while properties of the reaction products negatively affect the hygroscopicity of the powder mixture promoting disproportionation during longer-term storage. In addition, lubrication difference among three stearates was evaluated by performing compaction studies. The findings of this study provide an improved understanding of the proton transfer mechanism between the ionized form of an active pharmaceutical ingredient and excipients in solid dosage forms. It also provides pragmatic information for formulation scientists to select appropriate lubricants and other excipients, and to design robust formulations.

Characterization of palygorskite clay from Piauí, Brazil and its potential use as excipient for solid dosage forms containing anti-tuberculosis drugs

Clays play an important role in health products as it has been used as excipients for solid dosage forms and as active ingredients. Usually, excipients are pharmacologically inert, but they can interact with drugs in the solid dosage form and affect their bioavailability. Thus, the aim of this work was to determinate the physicochemical properties of palygorskite clay from Piaui, Brazil, and to investigate the potential use of this mineral as excipient for solid dosage forms containing rifampicin and isoniazid, which are drugs currently used to treat tuberculosis. Palygorskite was analyzed by X-ray fluorescence, X-ray diffraction, transmission electron microscopy, and particle size analyzer. According to the results, the main component found was SiO2, and its mineral composition contains palygorskite, dolomite, and quartz. The particles appear as fibers with bundle-like aspect that cluster together to form aggregates. The results from thermal analysis indicate that there is no interaction between both rifampicin and isoniazid with palygorskite. Moreover, the presence of palygorskite did not interfere on the dissolution of these drugs, which suggests that this material can be potentially used as an excipient for these drugs.

Modification of pharmacological activity of nebivolol due to Maillard reaction

Lactose is used as an excipient in solid dosage forms of nebivolol. Ultraviolet spectroscopy, Fourier-transform infrared spectroscopy and differential scanning calorimetry were used to study the interaction between nebivolol and lactose. The formation of a Maillard product was noted in aqueous mixtures of nebivolol and lactose heated at 60°C at unbuffered and buffered alkaline pH. A similar Maillard adduct formation was evident within 15 days in a dry physical mixture of nebivolol and lactose maintained at 40°C and 75% relative humidity in the dark. High-performance liquid chromatography and liquid chromatography–mass spectrometry analyses of the reaction mixtures confirmed the formation of a nebivolol–lactose adduct. The effects of intravenously administered nebivolol and the nebivolol–lactose adduct on the blood pressure and heart rate of anesthetized normotensive rats were investigated. The bradycardic effect of the adduct was significantly less than that of nebivolol. The present investigation reveals an incompatibility between nebivolol and lactose, leading to the loss of the pharmacological activity of nebivolol. Hence, the use of lactose as an excipient in dosage forms of nebivolol, a secondary amine, needs reconsideration.

Effect of moisture content, temperature and exposure time on the physical stability of chitosan powder and tablets

Context: Chitosan does not rank highly regarding its employment as tablet filler due to certain limitations. Undesirable properties that limit its utilization as excipient in solid dosage forms include its hydration propensity that negatively affects tablet stability, strength and disintegration.Objective: The objective of this study was to investigate the physical stability of chitosan powder, mixtures, granules and tablets under accelerated conditions such as elevated temperatures and humidity over different periods of time.Methods: Selected physico-chemical properties of pure chitosan powder, physical mixtures of chitosan with Kollidon® VA64 (BASF, Ludwigshafen, Germany), chitosan granules, as well as tablets were evaluated under conditions of elevated humidity and temperature.Results and discussion: The physical stability of chitosan tablets exhibited sensitivity towards varying exposure conditions. It was furthermore evident that the presence of moisture (sorbed water) had a marked influence on the physical stability of chitosan powder and tablets. It was evident that the presence of Kollidon® VA64 as well as the method of inclusion of this binder influenced the properties of chitosan tablets. The physical stability of chitosan powder deteriorated to a greater extent compared to that of the chitosan tablets, which were subjected to the same conditions.Conclusion: It is recommended that tablets containing chitosan should be stored at a temperature not exceeding 25 °C as well as at a relatively low humidity (<60%) to prevent deterioration of physical properties. Direct compression of chitosan granules which contained 5%w/w Kollidon® VA64 produced the best formulation in terms of physical stability at the different conditions.

Physicochemical and mechanical characterization of galactomannan from Mimosa scabrella: Effect of drying method

The galactomannan from Mimosa scabrella Bentham was extracted on a pilot plant scale and dried either by vacuum oven (GVO) or by spray-drier (GSD) to evaluate the effect of the drying technique on the powder quality and its applicability as excipient in solid dosage forms. The analysis by high performance size exclusion chromatography (HPSEC) coupled to multiangle laser light scattering (MALLS) suggests that both products behave as semi-flexible polymers, although the GSD showed more aggregation at molecular level (∼10%) and higher chain stiffness (Lp 9.1 nm). TG and DSC analysis showed weight loss event with peak at 299.7 and 311.9 °C to GVO and GSD, respectively, as well and higher ash content for GSD sample, in both inert and oxidant atmosphere. The X-ray diffraction confirmed the amorphous nature of both galactomannans although GVO showed high crystallinity. The GSD showed lower density (1.009 g/cm 3), higher cohesiveness (repose angle 35.5°, compressibility 32.2% and absence of flow), smaller and more spherical particles than GVO sample, both with high polydispersion. As vacuum oven-drying resulted in a like fibrous material, spray-drying appears as an alternative method easy to extrapolate in industry, requiring a glidant incorporation to improve the powder flowability.

Compatibility studies between piroxicam and pharmaceutical excipients used in solid dosage forms

Differential scanning calorimetry (DSC) with the support of Fourier transform infrared spectroscopy (FT-IR) was used as a screening technique for testing the compatibility of piroxicam (4-hydroxy-2-methyl-N-(2-pyridyl)-2H-1,2-benzothiazine-3carboxamide-1,1-dioxide) with various pharmaceutical excipients for solid dosage forms. Based on the results, magnesium stearate, stearic acid, and mannitol were found to show interaction with piroxicam. In conclusion, tools of DSC and FT-IR were successfully employed to evaluate the compatibility of piroxicam and selected excipients.

Thermal analysis study of the interactions between acetaminophen and excipients in solid dosage forms and in some binary mixtures

Thermogravimetry (TG) and differential scanning calorimetry (DSC) were used to assess the compatibility between acetaminophen (Ac) and some excipients (polyvinylpyrrolidone (P), magnesium stearate (M), citric acid (C), aspartame (As), mannitol (Mn), cellulose (Cll) and starch (S)) in several of the more commercially available pharmaceutical formulations and in solid binary mixtures. The present study compared thermodynamic data on acetaminophen melting and vaporization processes of pure acetaminophen with those found for several solid mixtures and in some commercially available acetaminophen-based dosage forms. Appreciable modifications occur only for solid mixtures with high content of excipient. Acetaminophen-based dosage forms and its solid binary mixtures usually show “additivity” of calorimetric peaks number of pure components in their calorimetric curve profiles, thus revealing a good thermoanalytical compatibility between acetaminophen and the excipients examined, except for samples containing appreciable content of mannitol.

Differential scanning calorimetry in compatibility testing of picotamide with pharmaceutical excipients

Differential scanning calorimetry with the support of X-ray powder diffractometry was used as a screening technique for testing the compatibility of picotamide (4-methoxy-N,N′-bis(3-piridinylmethyl)-1,3-benzenedicarboxamide) in the dehydrated form with various pharmaceutical excipients for solid dosage forms. The effect of dry grinding, wet grinding (i.e. kneading) and ageing on drug-excipient blends in the 1:1 (by weight) ratio on physicochemical and chemical stability of the drug was investigated. Chemical compatibility was in general observed with exception of combinations with tartaric and ascorbic acid, where acid/base interactions induced by heating were responsible for the drug degradation evidenced by the profound modification of the thermal effects of individual components. Analogous modifications (i.e. loss of melting peak of the drug) in mixtures with polyvinylpyrrolidone were due to amorphization of picotamide with no substantial alteration of its chemical integrity. Physical compatibility was seen in the systems with microcrystalline cellulose, corn starch, hydroxypropylmethylcellulose and hydroxyethylcellulose where dehydrated picotamide was stable except under wet grinding conditions. In combinations with sodium carboxymethylcellulose, veegum and arabic gum solid-state phase transformation of dehydrated picotamide to monohydrate occurred also by simple blending, probably because of the weak interaction between excipient and the associated water.

The effect of country of origin on the properties of dicalcium phosphate dihydrate powder

Five brands of dicalcium phosphate dihydrate powder manufactured in Germany, Japan, Spain, U.K. and U.S.A. have been characterized by X-ray diffraction, IR, DSC and TGA. Results on dehydration behaviour showed the Japanese material to be significantly more stable than the other four materials. SEM and laser scattering results showed these other four materials to be very similar, and to differ from the Japanese material, as regards micromeritic characteristics. Differences in specific surface values, as measured by adsorption of nitrogen, are related to particle size and intraparticle porosity. The above differences give rise to differences in their compression and flow properties, which could be relevant to the use of these products as excipients for solid dosage forms.