Comparative evaluation of soy polysaccharide as direct compression excipient

Abstract

Commercial soy polysaccharide (Emcosoy^R) has been evaluated as direct compression excipient in comparison with two frequently used materials, microcrystalline cellulose (Avicel pH 101) and pregelatinized maize starch (Sta-RX 1500).

Moisture sorption and desorption data analysed according to the Young and Nelson and the GAB equations and mechanical properties such as tensile strength, brittle fracture probensity, interparticle bonding isotropy and yield pressure of compacted excipients after storage at various environmental relative humidities are reported. Tableting characteristics such as punch force ratio, weight variation, tensile strength, friability, capping tendency, disintegration and dissolution of mixtures of the excipients and paracetamol are compared.

Emcosoy has been found to behave like Avicel as direct compression binder but like Sta-RX as disintegrant.     

Spray-dried chitosan as a direct compression tableting excipient

The objective of this study was to prepare and evaluate a novel spray-dried tableting excipient using a mixture of chitosan and lactose. Three different grades of chitosan (low-, medium-, and high-molecular-weight) were used for this study. Propranolol hydrochloride was used as a model drug. A specific amount of chitosan (1, 1.9, and 2.5 g, respectively) was dissolved in 50 mL of an aqueous solution of citric acid (1%) and later mixed with 50 mL of an aqueous solution containing lactose (20, 19.1, and 18.5 g, respectively) and propanolol (2.2 g). The resultant solution was sprayed through a laboratory spray drier at 1.4 mL/min. The granules were evaluated for bulk density, tap density, Carr index, particle size distribution, surface morphology, thermal properties, and tableting properties. Bulk density of the granules decreased from 0.16 to 0.13 g/mL when the granules were prepared using medium- or high-molecular-weight chitosan compared with the low-molecular-weight chitosan. The relative proportion of chitosan also showed a significant effect on the bulk density. The granules prepared with 1 g of low-molecular-weight chitosan showed the minimum Carr index (11.1%) indicating the best flow properties among all five formulations. All three granules prepared with 1 g chitosan, irrespective of their molecular weight, showed excellent flow properties. Floating tablets prepared by direct compression of these granules with sodium bicarbonate showed 50% drug release between 30 and 35 min. In conclusion, the spray-dried granules prepared with chitosan and lactose showed excellent flow properties and were suitable for tableting.     

Evaluation of emcocel® 50 and emcocel® 90, a new excipient in direct compression

The tabletting properties of a new microcrystalline cellulose product, Emcocel® 50 and Emcocel® 90 were evaluated and compared with the tabletting properties of Avicel® PH 101. The evaluation of placebo tablets, of the dilution potential, of formulations with active compounds as Aspirin, Phenobarbital and a spraydried extract in high concentrations showed that Emcocel® has comparative tabletting properties in regard of Avicel® PH 101.     

Ultrasound-assisted preparation of novel ibuprofen-loaded excipient with improved compression and dissolution properties

Context: Most of the active pharmaceutical ingredients (APIs) suffer from a drawback of poor aqueous solubility. In addition to the same, some APIs show poor tabletting behavior creating problems in formulation development. Crystal engineering can be an efficient tool in rectification of such problems associated with the APIs. Thus present work deals with crystallization of ibuprofen (a model drug) onto the surface of dicalcium phosphate (DCP) particles using different techniques.

Objective: The objective of the present work was to prepare ibuprofen-loaded DCP particles and further to analyze them for compressibility and dissolution behavior.

Materials and methods: Various crystallization techniques such as solvent evaporation (SE), melt crystallization (MC), melt sonocrystallization (MSC), antisolvent crystallization (AC), and antisolvent sonocrystallization (ASC) were screened for the preparation of ibuprofen-loaded DCP. Products obtained from different techniques were analyzed for physicochemical, micromeritic and compression properties.

Results and discussion: ASC technique was found to be suitable for preparing directly compressible ibuprofen-loaded DCP particles. The change in the crystal habit (needle to plate shape) of ibuprofen and its crystallization in miniscular form onto the surface of DCP particles showed significant improvement in the dissolution rate and compression properties of ibuprofen due to an increase in specific surface area when compared with ibuprofen crystallized by other techniques. Additionally, the tablets prepared from ASC powder did not require binder since ibuprofen acted as melt binder during compression.

Conclusion: Directly compressible ibuprofen-loaded DCP particles can serve as an alternative for conventional ibuprofen tablets prepared by wet granulation technique.     

An in vitro evaluation of fenugreek mucilage as a potential excipient for oral controlled-release matrix tablet

A polysaccharide mucilage derived from the seeds of fenugreek, Trigonella foenum-graceum L (family Fabaceae) was investigated for use in matrix formulations containing propranolol hydrochloride. Methocel^® hypomellose K4M was used as a standard controlled release polymer for comparison purposes. In this study the effect of lactose on the release behaviour of propranolol hydrochloride from matrices formulated to contain the fenugreek mucilage also was investigated. An increase in concentration of the mucilage in matrices resulted in a reduction in the release rate of propranolol hydrochloride comparable to that observed with hypomellose matrices. The rate of release of propranolol hydrochloride from fenugreek mucilage matrices was mainly controlled by the drug:mucilage ratio. However, the mechanism of release from matrices containing drug:mucilage ratios of 1:1, 1:1.25, 1:1.5, and 1:2 remained the same. The kinetics of release, utilising the release exponent n, showed that the values of n were between 0.46-0.57 indicating that the release from fenugreek mucilage matrices was predominantly by diffusion. The presence of lactose in matrices containing mucilage increased the release rate of propranolol hydrochloride. This is due to a reduction in tortuoisity and increased pore size of channels caused by lactose through which propranolol diffuses and therefore diffusion of water into the tablet is facilitated.     

Evaluation of sorghum starch as a tablet excipient

The suitability of sorghum starch as a binder and disintegrant at various concentrations in diverse tablet formulations have been investigated. Sodium bicarbonate and calcium carbonate were used as soluble and insoluble inorganic medicinal substances in various tablet formulations.

The effect of sorghum starch on the physical properties of the tablets were compared with those formulated with maize starch using the same concentrations of binder and disintegrant under the same experimental conditions.

The observations show that sorghum starch can be used as binder and disintegrant in tablet formulations. The indication is that the starch exhibit about twice the disintegrant power and about the same binding efficacy compared to maize starch.     

Evaluation of dibutyrylchitin as new excipient for sustained drug release

Dibutyrylchitin (DBC), a lipophilic chitin diester, has been synthesized from chitin and butyric anhydride with methanesulfonic acid as catalyst. Exhaustive esterification of free alcoholic groups of chitin was assessed by FT-IR and (1)H-NMR spectroscopy. High degree of alkyl substitution allowed DBC to acquire an almost completely lipophilic character. Tablets of paracetamol and metformin employing DBC as major excipient, in comparison with starch, microcrystalline cellulose, lactose and polyvinylpyrrolidone, were prepared and rates of drug release were checked by dissolution test assays. DBC released drug at a lower rate than that of the other tested materials. A comparison study of rate release of metformin from DBC tablets and from metformin-hydroxypropyl methylcellulose prolonged release oral formulation available on the market has been also curried out. Under the same conditions and in the presence of the same amount of loaded drug, DBC released 64% of metformin whereas hypromellose-based tablets released 87%.     

Evaluation of dibutyrylchitin as new excipient for sustained drug release

Dibutyrylchitin (DBC), a lipophilic chitin diester, has been synthesized from chitin and butyric anhydride with methanesulfonic acid as catalyst. Exhaustive esterification of free alcoholic groups of chitin was assessed by FT-IR and ¹H-NMR spectroscopy. High degree of alkyl substitution allowed DBC to acquire an almost completely lipophilic character. Tablets of paracetamol and metformin employing DBC as major excipient, in comparison with starch, microcrystalline cellulose, lactose and polyvinylpyrrolidone, were prepared and rates of drug release were checked by dissolution test assays. DBC released drug at a lower rate than that of the other tested materials. A comparison study of rate release of metformin from DBC tablets and from metformin-hydroxypropyl methylcellulose prolonged release oral formulation available on the market has been also curried out. Under the same conditions and in the presence of the same amount of loaded drug, DBC released 64% of metformin whereas hypromellose-based tablets released 87%.     

Comparative tablet and rheological properties of new microcrystalline cellulose: direct compression and wet granulation methods.

The overall objective of this study was to compare the rheological properties and tablet characteristics of two new varieties of celluloses (Vivacel 101 and 102), recently produced and commercialized, with the classical varieties of celluloses (Avicel and Elcema). The results showed no significant differences in the rheological properties of Vivacel and Avicel, while significant differences were found between the two celluloses and Elcema. Furthermore, there were no statistically significant differences in the disintegration times and Td values of Vivacel and Avicel. In conclusion, it was found that these new celluloses offer all the known advantages of Avicel.     

Evaluation of polyvinyl alcohols as mucoadhesive polymers for mucoadhesive buccal tablets prepared by direct compression

The purpose of the present work was to evaluate polyvinyl alcohols (PVAs) as a mucoadhesive polymer for mucoadhesive buccal tablets prepared by direct compression. Various polymerization degree and particle diameter PVAs were investigated for their usability. The tensile strength, in vitro adhesive force, and water absorption properties of the tablets were determined to compare the various PVAs. The highest values of the tensile strength and the in vitro adhesive force were observed for PVAs with a medium viscosity and small particle size. The optimal PVA was identified by a factorial design analysis. Mucoadhesive tablets containing the optimal PVA were compared with carboxyvinyl polymer and hydroxypropyl cellulose formulations. The optimal PVA gives a high adhesive force, has a low viscosity, and resulted in relatively rapid drug release. Formulations containing carboxyvinyl polymer had high tensile strengths but short disintegration times. Higher hydroxypropyl cellulose concentration formulations had good adhesion forces and very long disintegration times. We identified the optimal characteristics of PVA, and the usefulness of mucoadhesive buccal tablets containing this PVA was suggested from their formulation properties.     

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.     

Application of a novel automatic disintegration apparatus for the development and evaluation of a direct compression rapidly disintegrating tablet

An automatic disintegration tester was developed and used to explore disintegration mechanism and times of rapidly disintegrating tablets. DT50, the time required for a tablet to decrease in its thickness by half, allowed an unbiased determination of disintegration time. Calcium silicate concentration, Explotab? concentration, DiPac?/Xylitab? ratio as fillers, and compression pressure were evaluated using a central composite model design analysis for their DT50, tensile strength, and friability. Tablets that could reasonably be handled (friability <10%) could be produced. The expansion coefficient (n) and the exponential rate constant (k) for disintegrating tablets, originally measured by Caramella et al. using force kinetics, could be determined from axial displacement data measured directly without the need to assume that disintegration force generation was indicative of changes in tablet volume. The n values of tablets containing calcium silicate, Ditab? and/or Xylitab?, magnesium stearate, and Explotab? suggested that the amount of Explotab? was not a significant factor in determining the disintegration mechanism; however, the type of disintegrant used did alter the n value. Primojel? and Explotab?, which are in the same class of disintegrants, exhibited similar DT50, n, and k. Polyplasdone? XL exhibited a much higher n, while yielding faster DT50, suggesting that its performance is more dependent on facilitating the interfacial separation of particles. AcDiSol? showed no apparent moisture sensitivity in regards to disintegration efficiency. The use of the novel apparatus proved to be useful in measuring disintegration efficiency of rapidly disintegrating tablets and in providing valuable information on the disintegration phenomena.     

Green isolation and physical modification of pineapple stem waste starch as pharmaceutical excipient

The waste of inedible parts of pineapple, particularly in tropical countries, contributes to environmental burden. This study aimed to utilize pineapple stem waste as a source of starch-based pharmaceutical excipient. The starch was isolated from pineapple stem waste using a simple process without applying harsh chemicals. The isolated starch (PSS) was then physically modified through gelatinization and spray drying to improve its physical properties. Starch characteristics were identified by FTIR, TGA, and XRD analysis. The SEM imaging showed morphological change with reduced surface roughness due to physical modification of the starch. Decreased crystallinity of modified starch (MPS) was confirmed by our XRD results: the peaks of A-type crystalline at 2θ of 13°, 15°, 18°, and 23° were present in PSS, yet mostly absent in MPS. Thermogravimetric analysis showed that MPS behaved differently from PSS and the degradation events occurred at lower temperature. When the starch was spray-dried without prior gelatinization process, the physicochemical characteristics of spray-dried starch resembled untreated starch. Moisture content in PSS (10.66%) decreased after gelatinization to 7.3%. Potential use of MPS was demonstrated by its powder flowability (Student’s t test, p?<?0.05), swelling capacity (Student’s t test, p?<?0.05), and compaction profile. In summary, our findings demonstrated that modified pineapple starch showed better physical characteristics and quite promising as a tablet binder and disintegrant.     

Processing-induced-transformations (PITs) during direct compression: impact of compression speeds on phase transition of caffeine

For pharmaceutical industry, understanding solid-phase transition of the active pharmaceutical ingredient (API) induced by the manufacturing process is a key issue. Caffeine was chosen as a model API since it exhibits a polymorphic transformation during tableting. This study investigated the impact of the compression speed on the phase transition of anhydrous Form I (CFI) into Form II. Tablets were made from pure CFI and binary mixtures of CFI/microcrystalline cellulose, with an electric press well instrumented at three different compression speeds (50, 500 and 4500?mm?min^?1). For each velocity of the mobile punch studied, tablets made from three compression pressures (50, 100 and 200?MPa) were analyzed. The determination of the CFI transition degree was performed using a Differential Scanning Calorimetry (DSC). The CFI transition degree was monitored during three months in order to obtain the transformation profile of the API in tablets and in uncompressed powder. The modeling of the profile with a stretched exponential kinetic law (Johnson–Mehl–Avrami model) was used for the identification of the transition mechanism. The direct compression process triggered the polymorphic transformation in tablet when a sufficient compression pressure is applied. The velocity of the punch did neither impact the transition degree just after compression nor the transformation profile. The transition mechanism remained driven by nucleation for several operating conditions. Consequently, the punch velocity is not a decisive process parameter for avoiding such phase transition in tableting. As already observed, the compression pressure did not influence the transition whatever the compression speed and the velocity.     

Evaluation of rapidly disintegrating tablets prepared by a direct compression method

To make rapidly disintegrating tablets with sufficient mechanical integrity as well as a pleasant taste, microcrystalline cellulose (MCC), Tablettose (TT), and cross-linked sodium carboxymethyl cellulose (Ac-di-sol) or erythritol (ET) were formulated. Tablets were made by a direct compression method [1]. Tablet properties such as porosity, tensile strength, and disintegration time were determined. The tensile strength and disintegration time were selected as response variables, tablet porosity and parameters representing the characteristics of formulation were selected as controlling factors, and their relation was determined by the polynomial regression method. Response surface plots and contour plots of tablet tensile strength and disintegration time were also constructed. The optimum combination of tablet porosity and formulation was obtained by superimposing the contour diagrams of tablet tensile strength and disintegration time. Rapidly disintegrating tablets with durable structure and desirable taste could be prepared within the obtained optimum region.     

Matrices of water-soluble drug using natural polymer and direct compression method

The objective of this research was to find an optimum Carrageenan matrix formulation with the desired drug release and physical properties prepared by direct compression. In order to achieve this, matrices containing 10% theophylline, different Carrageenan level, and different excipient were prepared and evaluated. A selected matrix containing 40% Carrageenan and lactose fast flo was tested for dissolution in three different dissolution media (distilled water, 0.1 N HCl, and phosphate buffer pH 7.4). The same formulation was also tested for dissolution at 50 rpm, 100 rpm, and 150 rpm, and using different dissolution apparatus (Apparatus 1 and 2).

All matrices showed a decrease in drug release as the polymer level was increased. Only Avicel PH-101 did not show any significant difference between matrices prepared with 30% and 40% polymer. At 10% polymer level, it appears that the type of diluent used controls the drug release. However, at high polymer level, 30% and 40%, it appears that the polymer level controls the drug release. Phosphate buffer pH 7.4 and 0.1 N HCl increase drug release and appear to increase Carrageenan solubility and decrease gel formation. Also, as the rotational speed of the apparatus was increased, the integrity of the gel layer was decreased, and the release of drug was increased. The drug release from Carrageenan matrices appears to follow the diffusion model for inert matrix up to 90 min. After 90 min, the drug release follows a zero-order model.

This study demonstrated that matrices using Carrageenan can be successfully prepared by direct compression.     

Fluidized-Bed agglomeration of acetaminophen; direct compression of tablets and physiologic availability

A novel process was developed for manufacturing acetaminophen in a free-flowing, directly compressible agglomerated form, involving spray agglomeration of acetaminophen powder with polyvinylpyrrolidone (PVP) in isopropyl alcohol as a bonding agent using a fluidized-bed granulator. Agglomerates prepared with 5% PVP yielded a free-flowing and compressible material. Upon lubrication with 0.5% magnesium stearate, the material was found to be directly compressible into tablets. To improve dissolution and tableting properties, the agglomerates were compressed into tablets after blending with varying weight ratios of microcrystalline cellulose/pregelatinized starch as a filler/disintegrant combination. The final stable tablet formulation consisted of agglomerates equivalent to 325 mg of acetaminophen, 2.1 mg of magnesium stearate, and the filler/disintegrant in a weight ratio of 70:30 to yield a tablet weight of 425 mg. Physical properties and dissolution profile of these tablets were comparable to those of a commercial acetaminophen tablet. Physiologic availability calculated using the urinary excretion method indicated half-lives of 2.0, 2.1, and 2.2 hours for control (acetaminophen powder), experimental tablet, and a marketed product, respectively.     

Synthesis and evaluation of ciprofloxacin-loaded carboxymethyl tamarind kernel polysaccharide nanoparticles

Nanotechnology is currently employed as a tool to fight more efficiently against human pathogens. Nanoparticles can be prepared from a variety of materials such as protein, biodegradable polymers and synthetic polymers. Tamarindus indica Linn. or tamarind is one of the most important biodegradable polymer. In the present study, chemically modified polymer of tamarind ‘carboxymethyl tamarind kernel polysaccharide’ (CMTKP) is used for the synthesis of nanoparticulate formulation. Antibacterial activity of CMTKP was analysed which was then enhanced by incorporating a flouroquinolone antibiotic, ciprofloxacin to it. Ciprofloxacin-loaded CMTKP nanoparticles were synthesised via ionotropic gelation technique. Nanosuspension so formed was lyophilised by addition of a cryoprotectant. Nanoparticles obtained were characterised for its particle size, morphology and stability. Interaction studies were confirmed by Fourier transform infrared spectroscopy (FT-IR). Antibacterial activities of ciprofloxacin, CMTKP and ciprofloxacin-loaded CMTKP nanoparticles were tested against two Gram negative and positive bacteria. The antibacterial assay results revealed greatest zone of inhibition by ciprofloxacin-loaded CMTKP nanoparticles in Micrococcus luteus. Toxicity analysis of the prepared formulation was carried out on vero cell lines via resazurin assay which revealed its minimum toxicity.     

Co-proccessed excipients with enhanced direct compression functionality for improved tableting performance

It is necessary to have excipients with excellent functional properties to compensate for the poor mechanical properties and low aqueous solubility of the emerging active ingredients. Therefore, around 80% of the current drugs are not suitable for direct compression and more advanced excipients are required. Further, conventional grades of excipients cannot accommodate the technologically advanced high speed rotary tablet presses which require a powder with excellent flow, good compressibility, compactibility, particle size distribution and homogeneity of the ingredients. Co-processed excipients have been created to enhance the functional properties of the excipients and reduce their drawbacks. Co-processing is defined as the combination of two or more excipients by a physical process. Co-processed excipients are adequate for direct compression since they become multifunctional and thus, their dilution potential is high eliminating the need for many excipients in a formulation. In some cases, they are able to hold up to 50% of the drug in a formulation rendering compacts of good tableting properties. This study describes and discusses the functionality enhancement of commercial and investigational excipients through co-processing.