Tablet Thickness Research Articles

Study of the Validity of the Three-Point Bending Test for Pharmaceutical Round Tablets Using Finite Element Method Modeling

Mechanical strength is an important quality attribute of the tablets produced in the pharmaceutical industry. The three-point bending test is one of the methods described by the United States (US) pharmacopeia to test this property. In this work, finite element method modeling was perform to study the stress distribution in a round, flat tablet submitted to this test and to verify whether the equation given by US pharmacopeia to calculate the tensile strength could be used without restrictions. For this test, the center of the lower face of the tablet was submitted to the highest tensile stress and, at this point, the stress state was nearly uniaxial. This test is thus well suited to measure the tensile strength of pharmaceutical tablets. Moreover, simulations were performed with a large range of geometrical dimensions using the dimensionless parameters D/L and h/D (where D is the tablet diameter, h is the tablet thickness, and L is the distance between the supports). In order to obtain the value of the tensile strength with a good precision when using the equation given by the US pharmacopeia, the measurements should only be performed in a restricted area of the domain defined by D/L and h/D.

Sustain Release Formulation and Evaluation of Ofloxacin Floating Delivery System

Floating tablets has been accepted as a process to achieve controlled drug delivery by prolonging the residence time of the dosage form at the site of absorption, thereby improving and enhancing the bioavailability of drug. The objective of present study outlines the development and characterization the floating drug delivery system of Ofloxacin to enhance its bioavailability and therapeutic efficacy, using different grades of polymer along with effervescent agent sodium bicarbonate and citric acid. Ofloxacin is a synthetic chemotherapeutic second-generation antibiotic of the fluoroquinolone class. Different tablet formulations were formulated by wet granulation technique and were evaluated for physical parameters like Tablet Thickness, Hardness, % Friability, Weight variation, Content uniformity, In vitro buoyancy, Swelling index, In vitro dissolution study and drug release mechanisms. As the concentration of the polymer in the formulations increased the release of drug decreased. Hence it was considered as suitable candidate for formulation as floating drug delivery system. Different kinetic models were applied to drug release data in order to evaluate release mechanisms and kinetics. The optimized formula F4 showed better sustained drug release with good floating properties and fitted best to be Korsmeyer-Peppas model with R2 value of 0.9575. As the n value for the Korsmeyer- Peppas model was found be more than 0.5 it follows Non-Fickian diffusion mechanism. FTIR result showed that there is no drug excipients interaction.

Sustain Release Formulation and Evaluation of Ofloxacin Floating Delivery System

Floating tablets has been accepted as a process to achieve controlled drug delivery by prolonging the residence time of the dosage form at the site of absorption, thereby improving and enhancing the bioavailability of drug. The objective of present study outlines the development and characterization the floating drug delivery system of Ofloxacin to enhance its bioavailability and therapeutic efficacy, using different grades of polymer along with effervescent agent sodium bicarbonate and citric acid. Ofloxacin is a synthetic chemotherapeutic second-generation antibiotic of the fluoroquinolone class. Different tablet formulations were formulated by wet granulation technique and were evaluated for physical parameters like Tablet Thickness, Hardness, % Friability, Weight variation, Content uniformity, In vitro buoyancy, Swelling index, In vitro dissolution study and drug release mechanisms. As the concentration of the polymer in the formulations increased the release of drug decreased. Hence it was considered as suitable candidate for formulation as floating drug delivery system. Different kinetic models were applied to drug release data in order to evaluate release mechanisms and kinetics. The optimized formula F4 showed better sustained drug release with good floating properties and fitted best to be Korsmeyer-Peppas model with R2 value of 0.9575. As the n value for the Korsmeyer- Peppas model was found be more than 0.5 it follows Non-Fickian diffusion mechanism. FTIR result showed that there is no drug excipients interaction.

Development of New Shaped Punch to Predict Scale‐up Issue in Tableting Process

AbstractScale‐up issues in the tableting process, such as capping, sticking, or differences in tablet thickness, are often observed at the commercial production scale. A new shaped punch, named the size adjusted for scale‐up (SAS) punch, was created to estimate scale‐up issues seen between laboratory scale and commercial scale tableting processes. The SAS punch's head shape was designed to replicate the total compression time of a laboratory tableting machine to that of a commercial tableting machine. Three different lubricated blends were compressed into tablets using a laboratory tableting machine equipped with SAS punches, and any differences in tablet thickness or capping phenomenon were observed. It was found that the new shaped punch could be used to replicate scale‐up issues observed in the commercial tableting machine. The SAS punch was shown to be a useful tool to estimate scale‐up issues in the tableting process. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:235–240, 2014

Organic interlamellar layers, mesolayers and mineral nanobridges: Contribution to strength in abalone (Haliotis rufescence) nacre

The contributions of mesolayers, organic interlamellar layers and nanoasperities/mineral bridges to the strength of nacre from red abalone (Haliotis rufescens) shell nacre are investigated. Samples were demineralized and deproteinized to separate the organic and mineral components, respectively. Tensile tests were performed on both the isolated organic constituent and the isolated mineral. The strength of the isolated organic component suggests that growth bands play an important role in the mechanical behavior as they are thick regions of protein that are a significant fraction (∼0.4) of the total organic content. The thickness variation of the nacre tablets was measured and found to be a small fraction of the mean tablet thickness (0.568μm); the standard deviation is 26nm, indicating that the wedge mechanism of toughening does not operate in the nacre investigated. Results obtained from the isolated mineral validate the importance of the organic constituent as the mechanical properties decline greatly when the organic component is removed. The results presented herein add to the understanding of the mechanical response of the organic interlayers and growth bands and their effect on the toughness of the abalone nacre.

Distribution of a viscous binder during high shear granulation—Sensitivity to the method of delivery and its impact on product properties

Binder distribution in the powder mass during high shear granulation is especially critical with the use of viscous liquid binders and with short processing times. A viscous liquid binder was delivered into the powder mass at two flow rates using three methods: pouring, pumping and spraying from a pressure pot. Binder content analyses at the scale of individual granules were conducted to investigate the impact of different delivery conditions on the homogeneity of binder distribution. There was clear evidence of non-uniformity of binder content among individual granules across all delivery conditions, particularly for the fast rates of delivery. Poorer reproducibility values of tablet thickness and disintegration time were observed when binder was poured but this may be overcome by pumping or spraying from the pressure pot. Greater homogeneity of binder distribution occurred with the slow rates of delivery and led to the earlier onset of granule growth and a consequent increase in granule size. Larger granule size and lower proportion of fines were in turn associated with increased granule bulk density and improvement of granule flow. In conclusion, delivery of a viscous binder at a slow rate either by pumping or via a pressure pot was most desirable during granulation.

An index for evaluating difficulty of Chewing Index for chewable tablets

Chewing difficulty index, a potential measure of difficulty in chewing the chewable tablets, has been described herein as the product of tablet thickness and tablet hardness measured under the diametral loading. The proposed index was evaluated by measuring the dimensions and mechanical strength of commercial and in-house prepared chewable tablets. Data collected on tablets with different thickness but same hardness or tensile strength suggests that the proposed index provides a good assessment of the force needed to chew the chewable tablets. Influence of brief exposure to salivary fluid during chewing on the mechanical strength of the chewable tablets was also evaluated. Thirty seconds exposure to the simulated salivary fluid was also found to significantly reduce (p < 0.05) the hardness and the chewing difficulty index of a number of evaluated chewable tablet drug products.

FORMULATION AND EVALUATION OF BILAYER TABLET OF CANDESARTAN AND HYDROCHLOROTHIAZIDE FOR THE TREATMENT OF HYPERTENSION

The main purpose of this study was to design bilayered sustained release tablet of Candesartan and Hydrochlorothiazide to provide renoprotection in hypertension. The bilayered tablet was prepared by using super disintegrant Cross Carmellose,starch sodium glycolate,crosspovidone for Hydrochlorothiazide to provide its immediate release and Candesartan was made sustained released by using HPMC K4,K15 polymer.lactose is used as diluents. The prepared different layer were characterized by different parameters like angle of repose, bulk density, tapped density, compressibility index, moisture content .The prepared bilayered tablet was characterized by physical and chemical parameters such as tablet thickness, hardness, diameter, weight variation, drug content, friability and in vitro drug release. The present studies concluded that bilayered tablet of Candesartan and Hydrochlorothiazide is novel approach to prevent hypertension.

Investigations into the tensile failure of doubly-convex cylindrical tablets under diametral loading using finite element methodology

In the literature various solutions exist for the calculation of the diametral compression tensile strength of doubly-convex tablets and each approach is based on experimental data obtained from single materials (gypsum, microcrystalline cellulose) only. The solutions are represented by complex equations and further differ for elastic and elasto-plastic behaviour of the compacts. The aim of this work was to develop a general equation that is applicable independently of deformation behaviour and which is based on simple tablet dimensions such as diameter and total tablet thickness only. With the help of 3D-FEM analysis the tensile failure stress of doubly-convex tables with central cylinder to total tablet thickness ratios W/D between 0.06 and 0.50 and face-curvature ratios D/R between 0.25 and 1.85 were evaluated. Both elastic and elasto-plastic deformation behaviour were considered. The results of 80 individual simulations were combined and showed that the tensile failure stress σt of doubly-convex tablets can be calculated from σt=(2P/πDW)(W/T)=2P/πDT with P being the failure load, D the diameter, W the central cylinder thickness, and T the total thickness of the tablet. This equation converts into the standard Brazilian equation (σt=2P/πDW) when W equals T, i.e. is equally valid for flat cylindrical tablets. In practice, the use of this new equation removes the need for complex measurements of tablet dimensions, because it only requires values for diameter and total tablet thickness. It also allows setting of standards for the mechanical strength of doubly-convex tablets. The new equation holds both for elastic and elasto-plastic deformation behaviour of the tablets under load. It is valid for all combinations of W/D-ratios between 0.06 and 0.50 with D/R-ratios between 0.00 and 1.85 except for W/D=0.50 in combination with D/R-ratios of 1.85 and 1.43 and for W/D-ratios of 0.40 and 0.30 in combination with D/R=1.85. FEM-analysis indicated a tendency to failure by capping or even more complex failure patterns in these exceptional cases. The FEM-results further indicated that in general W/D-ratios between 0.15 and 0.20 are favourable when the overall size and shape of the tablets is modified to give maximum tablet tensile strength. However, the maximum tensile stress of doubly-convex tablets will never exceed that of a flat-face cylindrical tablet of similar W/D-ratio. The lowest tensile stress depends on the W/D-ratio. For the thinnest central cylinder thickness, this minimum stress occurs at D/R=0.50; for W/D-ratios between 0.10 and 0.20 the D/R-ratio for the minimum tensile stress increases to 0.67, and for all other central cylinder thicknesses the minimum tensile stress is found at D/R=1.00.

FEM simulation of the die compaction of pharmaceutical products: Influence of visco-elastic phenomena and comparison with experiments

This work studies the influence of visco-elastic behavior in the finite element method (FEM) modeling of die compaction of pharmaceutical products and how such a visco-elastic behavior may improve the agreement between experimental and simulated compression curves. The modeling of the process was conducted on a pharmaceutical excipient, microcrystalline cellulose (MCC), by using Drucker-Prager cap model coupled with creep behavior in Abaqus(®) software. The experimental data were obtained on a compaction simulator (STYLCAM 200R). The elastic deformation of the press was determined by performing experimental tests on a calibration disk and was introduced in the simulation. Numerical optimization was performed to characterize creep parameters. The use of creep behavior in the simulations clearly improved the agreement between the numerical and experimental compression curves (stresses, thickness), mainly during the unloading part of the compaction cycle. For the first time, it was possible to reproduce numerically the fact that the minimum tablet thickness is not obtained at the maximum compression stress. This study proves that creep behavior must be taken into account when modeling the compaction of pharmaceutical products using FEM methods.

Wireless transmission of ultrasonic waveforms for monitoring drug tablet properties and defects

The geometric and mechanical properties of pharmaceutical materials are crucial to their structural, functional and therapeutic effectiveness. The implementation of automated and convenient quality monitoring procedures is an attempt to balance control of quality against the level of testing; within acceptable levels of probability and costs. The capability of rapid/extensive inspections with minimal time and manufacturing interruption make non-contact quality monitoring systems a desirable approach to optimize this balance. In the current study, a wireless transceiver proof of concept system developed for the real-time quality monitoring of tablets during compaction is presented and demonstrated. The effectiveness of ultrasonic wave transmission through the punch-tablet interface is the boundary condition that dictates the viability of the acoustic in-die compaction monitoring approach. These measurements in the current experimental set-up can be used in determining various mechanical and geometric properties of a compact, such as the tablet thickness, mass density, elasticity and/or integrity of the tablet core, and bonding quality between layers depending on the given parameters, as it is compacted. In the current study, it is demonstrated that the reflection of an ultrasonic pulse generated by a transducer embedded in an upper punch from the lower punch-tablet interface can be acquired by the same transducer in the upper punch and the analog waveform can be transmitted to a computer by means of wireless communications for further signal processing and property extraction. The evolution of apparent Young's moduli of a powder bed during a full-compaction cycle is derived from the ultrasonic time of flight of an acoustic waveform acquired during compaction in-die.

Using Terahertz Reflectance Spectroscopy to Quantify Drug Substance in Tablets

The purpose of this research is to investigate the applicability of terahertz (THz) reflectance spectroscopy for quantification of drug substance in tablets, so as to demonstrate the feasibility for applying this technique to tableting process monitoring. In order to acquire a suitable absorbance spectrum for this purpose, it was necessary to enhance the reflection intensity. By using an aluminum plate as a mirror at the opposite surface of the tablet, a reasonable absorbance spectrum could be acquired to reflect the bulk information of the tablet. To assess the limit of tablet thickness, linearity between the tablet thickness and the absorbance value was investigated using lactose and mannitol tablets. Since linearity was found within 0.75-5.0 mm for both tablets using 0.4 and 0.8 THz region, it was confirmed that THz reflectance spectroscopy is applicable to tablets within at least 5.0 mm thickness. Mannitol tablets containing sodium salicylate as the model drug substance were used to investigate the quantitative performance of this technique. It was confirmed that the established calibration model was acceptable for this quantification because of the root-mean-squared error of cross-validation (RMSECV) being 1.95%. In order to evaluate the applicability of this technique, content quantitative performance in double layered tablets having active and placebo layers were assessed. Since this calibration model achieved the root-mean-squared error of prediction (RMSEP) of 1.42% for the double layered tablets, this technique was considered feasible even if the drug substance is localized in the tablets.

Effects of Compaction Variables on Porosity and Material Tensile Strength of Convex-faced Aspirin Tablets

The porosity and tensile strength of convex-faced aspirin tablets formed under a compaction pressure in the range 40-320 MPa and at punch velocities in the range 0.008 to 500 mm s-1 have been determined. The material tensile strength, sigma f, was calculated from the observed fracture load, Ps, using the equation of Pitt et al (1988): sigma f = 10 Ps/pi D2(2.84 t/D - 0.126 t/W + 3.15 W/D + 0.01)-1 where D is the tablet diameter, t is the overall tablet thickness and W is the central cylinder thickness. Tablets formed at lower compaction pressures had a higher porosity and lower tensile strength than those formed at higher compaction pressures. Tablets of face curvature ratio (D/R) in the range 0.25-0.67 and a normalized cylinder length (W/D) of 0.2 had the optimum tensile strength. (R is the radius of curvature of the tablet face.) Tablets formed at high compaction rates were significantly weaker than those formed at lower compaction rates.

The properties of tablets manufactured on an automatically-controlled rotary machine.

Abstract Four direct-compression bases: Celutab in the hydrous and the anhydrous form, Emcompress Special, and spray-dried lactose, have been compared with a traditional lactose granulation with respect to initial physical properties of the powder, tabletting performance and the characteristics of the tablets produced. The tablets were made on an instrumented rotary machine with feedback weight control operating to minimize time-dependent change within a batch, compression force being continuously monitored. Tensile strength by diametral crushing, porosity, disintegration time and surface indentation hardness were assessed and correlated with changes in compaction force, machine speed and tablet thickness. All materials gave wellformed tablets with no evidence of capping between 90 and 350 MN m−2, and weight variation was small except for Emcompress Special at the highest machine speed, when die filling became erratic.

The Material Tensile Strength of Convex-faced Aspirin Tablets

The material tensile strength of a range of convex-faced tablets, compacted under controlled conditions at pressures of 40 and 320 MPa from a size fraction of acetylsalicylic acid, has been assessed. The calculation of the tensile strength sigma 1, from observed fracture loads obtained in diametral compression testing, is based on the equation derived by Pitt et al (1988), namely: (formula; see text) where P is the fracture load, D is the tablet diameter, t is the overall tablet thickness and W is the central cylinder thickness. The strength of a tablet of a given shape compacted at 320 MPa was between two and four times greater than that of a similar tablet compacted at 40 MPa. For the thicker tablets (W/D greater than or equal to 0.2) the material tensile strength was practically independent of shape. For the thinner tablets (W/D = 0.1) the material tensile strength varied considerably with face-curvature, showing a maximum for each of the two compaction pressures at a D/R value of 0.67.

Computer analysis of the relation between tablet strength and compaction pressure.

Abstract The load necessary to fracture lactose monohydrate tablets under diametral compression has been determined using an Instron physical testing instrument, so that true tensile failure was obtained in all cases, leading to improved reproducibility. Four ranges of tablet thickness were examined at 12·7 mm diameter. All tablets gave a linear increase of breaking load with compaction pressure up to 310 MN/m2. Expressing the tablet strength as the breaking load gave a separate regression line for each range of tablet thickness, whereas the use of tensile strength provided a common regression line, within given statistical limits, for all but the lowest range of tablet thickness. The fact that such a correlation is possible shows that the tensile strength is a property of the “as compacted” material and provides a new and useful parameter to maintain constancy of properties when tablet size is changed.

In vitro and in vivo evaluation of hydrophilic and hydrophobic polymers-based nicorandil-loaded peroral tablet compared with its once-daily commercial sustained-release tablet

Context: Hydrophilic and hydrophobic polymer-based nicorandil (10 mg)-loaded peroral tablets were prepared using the wet granulation technique. The influence of varying amounts of hydroxypropyl methylcellulose (HPMC) (30–50 mg), ethylcellulose (2–4 mg), microcrystalline cellulose (5–20 mg) and Aerosil® (5–12 mg) in conjunction with the constant amounts (3 mg) of glidant and lubricant (magnesium stearate and talc) on the in vitro performances of the tablets (hardness, friability, weight variation, thickness uniformity, drug content, and drug release behavior) were investigated. Objective: The objectives of this study were (i) to select a nicorandil-loaded peroral tablet that matched the in vitro dissolution profile of once-daily commercial sustained-release tablet, and (ii) to compare the in vivo sustaining/controlling efficacy of the selected peroral tablet with that of its commercial counterparts. Results and Discussion: Because the nicorandil (10 mg)-loaded tablet prepared based on F-IX composition (50 mg HPMC, 4 mg ethylcellulose, 10 mg MCC and 3 mg glidant and lubricant) showed a release profile comparable to that of the Nikoran® OD SR tablet release profile, the tablet with this composition was considered to be the optimized/selected formulation and, therefore, was subjected to stability study and in vivo study in rabbits. Despite of the higher Cmax and AUC values obtained with the optimized tablet, there was no sign of difference between the optimized- and Nikoran® OD SR- tablets following a single-dose crossover oral administration into rabbit. Conclusion: The optimized tablet could be used as an alternative to the commercial once-daily tablet.

Oxycellulose as mucoadhesive polymer in buccal tablets

Background: Oxycellulose (OC) is biodegradable and bioabsorbable cellulose derivative used in medicine to support hemostasis and tissue healing. Recently, its antimicrobial and immunomodulating properties, as well as its potential in modern therapeutic systems as release modifying excipient, drug carrier, and/or mucoadhesive polymer, are widely discussed. Method: To study its last-mentioned characteristics, directly compressed tablets containing 5 mg of cetylpyridinium chloride (CPC) as a model drug and 90 mg of mucoadhesive polymer [oxycellulose sodium (NaOC) alone or in a combination with one of five widely used mucoadhesive polymers] were prepared to ensure 8 hours prolonged release of CPC. Physicochemical and mucoadhesive properties of prepared tablets were evaluated. Results: Based on obtained results, tablets containing OC in combination with hydroxypropylmethylcellulose (Methocel® K100LV) or carboxymethylcellulose sodium showed the best quality parameters (friability < 0.04%, tablet thickness < 2.17 mm, tablet hardness > 85 N, residence time > 256 minutes, mucoadhesive strength > 3.45 mN/mm) and dissolution profiles (more than 81% of CPC released within 8 hours). Conclusion: NaOC embodies excellent compressing, mechanical, and mucoadhesive properties; however, formulation with higher content of NaOC only showed shorter adhesion time (107 ± 7 minutes) and faster drug release (93.66% of CPC released within 2 hours), because of its good solubility in aqueous media.

Development of a method for nondestructive NIR transmittance spectroscopic analysis of acetaminophen and caffeine anhydrate in intact bilayer tablets

Calibration models for nondestructive NIR analysis of API (active pharmaceutical ingredient) contents in two separate layers of intact bilayer tablets were established. These models will enable the use of NIR transmittance spectroscopy in bilayer tableting processes for the control of API contents in separate layers. Acetaminophen and caffeine anhydrate were used as APIs, and tablets were made by the direct compression method. Their NIR spectra were measured in the transmittance mode. The reference assay was performed by HPLC. Calibration models were generated by the partial least-squares (PLS) regression. The initial calibration generated models with insufficient linearity and accuracy because the fluctuation range of tablet thickness was excessively large and irrelevant information on the thickness fluctuation was included in the models. By narrowing the fluctuation range to determine the proper range for acceptable prediction accuracy, it was confirmed that calibration models with less irrelevant information can be generated when the range was 4.30 ± 0.06 mm or narrower. Furthermore, the fluctuation range of 4.30 ± 0.06 mm was considered to be empirically valid in covering the fluctuation actually observed in ordinary tableting processes. Thus, the sample tablets within this range were used to generate the final calibration models, and calibration models sufficient in linearity and accuracy were established. In addition, it was proven that controlling the irradiated side was unnecessary. Namely, it is not necessary to keep the same side of sampled tablets for the online NIR analysis during bilayer tableting. It is useful, in order to obtain adequate calibration models, to evaluate the variable factors that affect the linearity and accuracy of the generated models and restrict the range of models or use a subset of prepared samples. Loading vectors, explained variances, and correlation coefficients between components and scores are important for the evaluation of variable factors.

English

This research evaluated the physicochemical equivalence of some samples of Nifedipine 20 mg Retard Tablets available in Nigeria. Seven samples were randomly procured from various zones of the country and standard protocols applied to evaluate their tablet weight uniformity, dimensions, hardness, disintegration time, content of active Ingredient and in vitro drug release profile. Results showed that all the samples tested were chemically, but not physically equivalent. Although within each sample, compendial requirement for tablet weight uniformity was met, there were significant differences in the mean tablet weights, diameters and thickness of the samples studied (p < 0.05). Furthermore, tablet hardness and disintegration time varied much among the samples, but not within each sample. All the samples met the compendial requirement for content of active ingredient and released more than 80% of the drug within 4 h. It is therefore pertinent that manufacturers of this product be advised to formulate tablets that are equivalent in size, as different tablet sizes may impart negative psychological effects on clinicians and their patients when the need arises for switch over from one product to another, since the availability of particular products is never guaranteed at all times in Nigeria, a largely import dependent nation. Key words: Nifedipine 20 mg Retard tablets, physicochemical equivalence, in-vitrodrug release.