Tablet Erosion Research Articles

Development and evaluation of C10 and SNAC erodible tablets for gastric delivery of a GIP/GLP1 peptide in monkeys

The permeation enhancers (PEs) sodium caprate (C10) and sodium N-[8-(2-hydroxybenzoyl) amino] caprylate (SNAC) have been utilized for the intestinal and gastric delivery of macromolecules, respectively. However, the potential of C10 for the gastric delivery of a peptide and the ability of SNAC to deliver other peptides to the stomach beyond semaglutide have not been investigated. In this study, we have developed and evaluated C10 and SNAC-containing erodible tablets for the gastricdelivery of a glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GIP/GLP1) dual agonist peptide (LY) in cynomolgus monkeys. We also evaluated the impact of release rates on the in vivo performance of C10 and SNAC. Furthermore, we compared the oral exposure of the LY peptide and semaglutide with different proteolytic stabilities using a SNAC erodible tablet. Additionally, we investigated the mechanism of action of SNAC for improving gastric absorption of the LY peptide via tissue distribution in monkey. C10 and SNAC tablets released the peptide and PE by erosion from the tablet surface with 100 % release within 60 min at pH 6.8. Following a single oral administration to monkeys, C10 and SNAC erodible tablets at 300 mg exhibited similar LY mean absolute oral bioavailability of 5.7 % and 4.2 %, respectively. The C10 immediate release capsule (500 mg) with faster dissolution profile (10 min) showed a decrease in the LY oral bioavailability; however, a faster dissolution profile (15 min) with erodible SNAC tablet resulted in a relatively higher LY oral bioavailability compared to the slow-release erodible tablets (60 min). Using SNAC as the PE, the combination of slow-release tablet design and LY peptide with higher pepsin stability resulted in about 4-fold higher mean oral bioavailability in the monkeys than semaglutide (4.2 % vs 1.2 %, respectively). In the monkey gastric tissue, SNAC was found to reduce tight junction protein levels and increase the peptide uptake into the gastric epithelium suggesting its permeation enhancing mechanism via both paracellular and transcellular pathways. Taking these data altogether, the enhanced proteolytic stability of the LY peptide combined with the optimal erodible tablets enabled the gastric delivery of the LY peptide with a higher oral bioavailability than semaglutide.

Effect of matrix-forming agent ratios on drug release, water sorption and erosion behaviors of shellac wax-poloxamer matrix tablet

Shellac wax (SHW) is a natural, organic resin obtained from insects such as Laccifer lacca. Poloxamer (P) is synthesized tri-block copolymer consists of hydrophilic and hydrophobic blocks arranged in a tri-block structure. In this experiment, the matrix tablets comprising various ratios of P and SHW were fabricated with fusion method. Hydrophilic and hydrophobic model drugs in this study were propranolol hydrochloride (PRN) and hydrochlorothiazide (HCTZ), respectively. Water sorption and erosion behaviors and drug release patterns were investigated. Tablet weight and hardness was slightly increased as the content of P increased due to higher density of P than that of SHW. The swollen tablet was obtained when using higher amount of P. In contrast, tablet erosion was observed in matrix tablets comprising lower content of P. The swelling of matrix tablets comprising 7:3 and 8:2 of P: SHW ratios could promote the prolongation of the drug release; thus, they show the potential for using as the matrix base for controlled drug delivery systems.

Matrix tablets based on a novel poly (magnesium acrylate) hydrogel for the treatment of inflammatory bowel diseases

The objective of this work was to evaluate the potential use of a new polymer (PAMgA) in the development sustained release matrix tablets for the treatment of bowel inflammatory diseases. For this purpose, budesonide, a highly lipophilic compound, was used as model drug. Tablets with two reticulation grades of PAMgA (PAMgA 5 and 40) and with 9 mg of budesonide were developed and characterized. All the studies were carried out using biorelevant media (FaSSGF and FaSSIF).Swelling and erosion of PAMgA tablets was influenced by the reticulation grade of the polymer and the biorelevant media assayed, being water uptake higher for PAMgA 40 tablets in intestinal fluid, whereas PAMgA 5 showed more intense erosion in this biorelevant medium. Budesonide was released slowly from PAMgA tablets, both in gastric and intestinal environment, following Super case II transport kinetics (relaxation-controlled delivery), with a lag time of around 1–2 h. When the dissolution medium was changed sequentially throughout the trial, 75% of the budesonide dose was released in a sustained manner between 4 and 20 h of testing from PAMgA tablets, showing a more controlled budesonide release than Entocort® and Budenofalk® (commercially available sustained release formulations of budesonide). In conclusion, PAMgA polymer allows controlling the release of highly lipophilic drugs as budesonide, being an useful excipient for the development of sustained release matrix tablets.

Relationship Between Oral Semaglutide Tablet Erosion and Pharmacokinetics: A Pharmacoscintigraphic Study.

Semaglutide, a glucagon‐like peptide‐1 (GLP‐1) analogue, has been coformulated in a tablet with the absorption enhancer, sodium N‐(8‐[2‐hydroxybenzoyl] amino) caprylate (SNAC). We investigated tablet erosion and the pharmacokinetics of oral semaglutide administered with 2 different water volumes and evaluated the relationships between these parameters. In a randomized, single‐center (Quotient Sciences, UK), open‐label, 2‐period crossover trial, 26 healthy men received single doses of 10 mg oral semaglutide with 50 or 240 mL water while fasting. Tablet erosion and gastrointestinal transit were assessed by gamma scintigraphy. Semaglutide and SNAC plasma concentrations were measured until 24 and 6 hours, respectively, after administration. Complete tablet erosion (CTE) occurred in the stomach irrespective of water volume administered with the tablet (primary end point). Mean time to CTE was 85 versus 57 minutes with 50 versus 240 mL water (ratio 50/240 mL, 1.51; 95% confidence interval, 0.96‐2.37; P = .072). Area under the semaglutide concentration‐time curve from 0 to 24 hours (AUC0‐24h,semaglutide) and maximum semaglutide concentration (Cmax,semaglutide) were ∼70% higher with 50 versus 240 mL water (P = .056 and P = .048, respectively). Median time to maximum semaglutide concentration (tmax,semaglutide) was 1.5 hours independent of water volume with dosing. Higher AUC0‐24h,semaglutide and Cmax,semaglutide and longer tmax,semaglutide were significantly correlated with longer time to CTE and later gastric emptying of tablet and water (all P < .05). The safety profile was as expected for the GLP‐1 receptor agonist drug class. In conclusion, the oral semaglutide tablet erodes in the stomach irrespective of water volume with dosing. Slower tablet erosion in the stomach results in higher semaglutide plasma exposure.

Investigating the Influence of Tablet Location Inside Dissolution Test Apparatus on Polymer Erosion and Drug Release of a Surface-Erodible Sustained-Release Tablet Using Computational Simulation Methods.

The objective of this work was to investigate the influence of tablet location along the bottom of a USP apparatus II vessel on polymer erosion and drug release of surface-erodible sustained-release tablets using computational simulation methods. Computational fluid dynamics (CFD) methods were performed to simulate the velocity distribution. A mathematical model was developed to describe polymer erosion and tablet deformation according to the mass transfer coefficient. Numerical analysis was used to simulate drug release controlled by drug diffusion and polymer erosion. The results indicated that tablets located at the off-center position deformed faster than the tablets located at the center position. However, tablet location had no profound impact on drug release rate since all drug release profiles were "similar" according to the f2 similarity values which were above 50. Hence, our simulation supported that the USP apparatus II was a reliable and robust device for the dissolution testing of surface-erodible sustained-release tablets.

Systematic Studies on Surface Erosion of Photocrosslinked Polyanhydride Tablets and Data Correlation with Release Kinetic Models.

Photocrosslinkable polyanhydrides that undergo surface erosion are suitable materials for controlled-release drug delivery systems. Investigating the impact of different parameters on their erosion behavior is essential before use in drug delivery systems. Although their synthesis is well-established, parameters that may substantially affect the erosion of thiol-ene polyanhydrides including temperature and pH of the media, the geometry of the polymers, and the media shaking rate (the convective force for the polymer erosion), have not yet been studied. This study explores the effects of different environmental and geometric parameters on mass loss (erosion) profiles of polyanhydrides synthesized by thiol-ene photopolymerization. A comparative study on several release kinetic models fitting is also described for a better understanding of the polymer erosion behavior. The results demonstrated that although the temperature was the only parameter that affected the induction period substantially, the mass-loss rate was influenced by the polymer composition, tablet geometry, temperature, pH, and mass transfer (shaking) rate. With regard to geometrical parameters, polymers with the same surface area to volume ratios showed similar mass loss trends despite their various volumes and surface areas. The mass loss of polyanhydride tablets with more complicated geometries than a simple slab was shown to be non-linear, and the kinetic model study indicated the dominant surface erosion mechanism. The results of this study allow for designing and manufacturing efficient delivery systems with a high-predictable drug release required in precision medicine using surface-erodible polyanhydrides.

Controlled Release of Highly Hydrophilic Drugs from Novel Poly(Magnesium Acrylate) Matrix Tablets.

The potential of a new poly(magnesium acrylate) hydrogel (PAMgA) as a pharmaceutical excipient for the elaboration of matrix tablets for the extended release of highly hydrophilic drugs was evaluated. The polymer was synthetized with two different crosslinking degrees that were characterized by FTIR and DSC. Their acute oral toxicity was determined in a mouse model, showing no toxicity at doses up to 10 g/kg. Matrix tablets were prepared using metformin hydrochloride as a model drug and the mechanisms involved in drug release (swelling and/or erosion) were investigated using biorrelevant media. This new hydrogel effectively controlled the release of small and highly hydrophilic molecules as metformin, when formulated in matrix tablets for oral administration. The rate of metformin release from PAMgA matrices was mainly controlled by its diffusion through the gel layer (Fickian diffusion). The swelling capacity and the erosion of the matrix tablets influenced the metformin release rate, that was slower at pH 6.8, where polymer swelling is more intensive, than in gastric medium, where matrix erosion is slightly more rapid. The crosslinking degree of the polymer significantly influenced its swelling capacity in acid pH, where swelling is moderate, but not in intestinal fluid, where swelling is more intense.

Mechanical strength, structural and hydration properties of ethanol-treated starch tablets and their impact on the release of active ingredients

Ethanol-treated starch (ETS) shows potentiality to be used for binder of pharmaceutical tablets. This study was aimed to evaluate the mechanical strength, structural and hydration properties of ETS tablets and ETS tablets containing lauric acid and ascorbic acid and their release behavior. ETS was prepared from cassava starch at the temperatures of 80, 90, and 100 °C. The active compounds were entrapped within the ETS tablets by two methods, including dry mixing and ethanol solubilisation. The results indicated that ETS tablets from temperatures of 80 °C showed granular shapes, had high friability and low crushing strength indexes, and dispersed and released active ingredients rapidly upon contact with water. Meanwhile, ETS tablets from temperatures of 90 and 100 °C exhibited non-granular particles, had low friability and high crushing strength indexes. Upon hydration, the tablets of non-granular ETS containing lauric acid eroded gradually and released active ingredients during tablet's erosion, meanwhile ascorbic acid diffused out gradually from the swelled tablets.

FORMULATION AND OPTIMIZATION OF FLOATING TABLETS OF CLOPIDOGREL BISULPHATE USING DESIGN OF EXPERIMENTS

Objective: The present study aimed at designing of floating matrix tablet of clopidogrel bisulphate by design of experiments.Methods: The tablets were prepared by direct compression technique using hydroxypropyl methylcellulose K15 (HPMC) as a matrix polymer and sodium bicarbonate as a gas generating agent. In order to optimize the concentration of HPMC (X1) and sodium bicarbonate (X2), a 32 full factorial design was employed. The tablet formulations were evaluated for floating lag time (Y1), floating or buoyancy time (Y2), percent water uptake, and differential scanning calorimetry (DSC) and in vitro drug release (Y3).Results: The formulation variables, HPMC concentration, and sodium bicarbonate concentration exerted a significant effect on floating behavior and drug release characteristics of the tablet. The optimized formulation, with 15% sodium bicarbonate concentration and 30 % HPMC concentration resulted in 5±2.6 sec of floating lag time, 22.0±0.6 h of floating time and 42.0±0.99% of clopidogrel bisulphate release in 8 h of dissolution study. The drug release mechanism was identified as nonfickian. The water uptake studies revealed that with an increase in HPMC concentration, there was an increase in swelling index of tablet whereas higher sodium bicarbonate concentration supported the faster erosion of matrix tablets. DSC study revealed no interaction of drug and polymers. The lower percentage error between predicted and observed responses of the optimized formulation validated the design.Conclusion: The study demonstrated successful designing of floating clopidogrel bisulphate tablet with factorial design.

Investigation of the effects of excipients on technological properties tablets of pyrola rotundifolia extract

Aim of the work. To study the influence of excipients on the pharmacological and technological properties of round-leaved wintergreen extract tablets.Methods. The subject of the study were 27 series of round-leaved wintergreen extract tablets. The study of the influence of excipients on the pharmacological and technological properties of tablets, namely: abrasion, strength, disintegration, homogeneity were carried out in accordance with the requirements of SPhU 2 edition. The appearance of tablets of round-leaved wintergreen extract was estimated on a five-point scale.Results. The effect of 27 excipients on the pharmaco-technological indicators of the quality of tablets was studied during the creation of tablets by the method of direct compression. The experiments were done using the mathematical planning of the experiment – the Graeco-Latin square of the 2nd order.The results of the dispersion analysis of experimental data showed that the highest estimation of the appearance obtained tablets with neusilin US 2, vivapur 102, vivapur 112, pearlitol 100SD-mannitol.The best value for homogeneity of dosage of tablets with round-leaved wintergreen extract was obtained using potato starch, calcium anhydrous hydrogen phosphate, vivapur 302, pearlitol 300 DC-mannitol.The fastest breakdown tablets were round-leaved wintergreen extract with neusilin US 2, magnesium stearate, sodium croscarmellose, flovelaks, vivapur 200, MCC burst, vivapur 302.The greatest value of the strength of tablets with round-leaved wintergreen extract was obtained with sodium croscarmellose, tabletose 80, and procolv SMCC 90.Lowest erosion of tablets with round-leaved wintergreen extract provide neusilin US 2, calcium stearate, sodium croscarmellose, procolv EASYtab SP, tabletose 80.The generalized function of desirability allowed to select the optimal levels of factors (excipients) for each group of factors: neusilin US 2, magnesium stearate, sodium croscarmellose, procolv EASYtab SP, flovelaks.Conclusions. With the help of the Graeco-Latin square of the 2nd order, the influence of the 27th excipients on the pharmaco-technological properties of the tablets (appearance, homogeneity of dosage, disintegration , strength and erosion) and the generalized index – the function of desirability were studied. The experimental results allowed to select optimal excipients for further technological research

Using Computational Fluid Dynamics to Compare Shear Rate and Turbulence in the TIM-Automated Gastric Compartment With USP Apparatus II

We use computational fluid dynamics to compare the shear rate and turbulence in an advanced in vitro gastric model (TIMagc) during its simulation of fasted state Migrating Motor Complex phases I and II, with the United States Pharmacopeia paddle dissolution apparatus II (USPII). A specific focus is placed on how shear rate in these apparatus affects erosion-based solid oral dosage forms. The study finds that tablet surface shear rates in TIMagc are strongly time dependant and fluctuate between 0.001 and 360 s−1. In USPII, tablet surface shear rates are approximately constant for a given paddle speed and increase linearly from 9 s−1 to 36 s−1 as the paddle speed is increased from 25 to 100 rpm. A strong linear relationship is observed between tablet surface shear rate and tablet erosion rate in USPII, whereas TIMagc shows highly variable behavior. The flow regimes present in each apparatus are compared to in vivo predictions using Reynolds number analysis. Reynolds numbers for flow in TIMagc lie predominantly within the predicted in vivo bounds (0.01-30), whereas Reynolds numbers for flow in USPII lie above the predicted upper bound when operating with paddle speeds as low as 25 rpm (33).

ВИБІР ДОПОМІЖНИХ РЕЧОВИН З МЕТОЮ ОТРИМАННЯ ТАБЛЕТОК НА ОСНОВІ КАРБАМАЗЕПІНУ З ТІОТРИАЗОЛІНОМ МЕТОДОМ ВОЛОГОЇ ГРАНУЛЯЦІЇ

Мета роботи. Обгрунтувати доцільність створення комбінованого лікарського засобу на основі карбамазепіну з тіотриазоліном. Вивчити вплив ДР на процес пресування, якість поверхні та однорідність маси таблеток на основі карбамазепіну з тіотриазоліном, які отримували методом вологої грануляції.Матеріали і методи. Діючі речовини - карбамазепін з тіотриазоліном (1,5:1), допоміжні речовини (наповнювачі, розпушувачі, зв’язуючі, змазуючі). Таблетки пресували методом вологої грануляції. Вплив ДР речовин на таблетки карбамазепіну з тіотриазоліном вивчали за такими показниками: процес пресування, зовнішній вигляд поверхні таблеток після виготовлення, однорідність дозування маси таблеток.Результати й обговорення. За результатами дисперсійного аналізу експериментальних даних було встановлено, що на процес пресування, зовнішній вигляд поверхні таблеток після виготовлення та однорідність дозування маси таблеток карбамазепіну з тіотриазоліном впливає природа наповнювача, розпушувача, зв’язуючих та змазуючих ДР Так, на процес пресування таблеток серед наповнювачів найкращий вплив має МКЦ 101, серед розпушувачів лідером є крохмаль преджелатанізований.На якість поверхні таблеток карбамазепіну з тіотриазоліном після виготовлення серед розпушувачів найбільший позитивний вплив має крохмаль картопляний. На однорідність дозування маси таблеток серед змазуючих речовин лідером є кислота стеаринова, серед розпушувачів перевага на боці крохмалю преджелатанізованого, серед наповнювачів лідером є МКЦ 101, серед зв’язуючих найбільший вплив має 2 % розчин ГПМЦ.Висновки. Вивчено вплив чотирьох груп допоміжних речовин на процес пресування, зовнішній вигляд та однорідність дозування таблеток карбамазепіну з тіотриазоліном. Більшість із вивчених 16-ти ДР придатна для отримання таблеток карбамазепіну з тіотриазоліном методом вологої грануляції. За дослідженими показниками (процес пресування, якість поверхні таблеток, однорідність дозування) побудовані діаграми переваг рівнів вивчених факторів.

Release mechanism of doxazosin from carrageenan matrix tablets: Effect of ionic strength and addition of sodium dodecyl sulphate

The polyelectrolyte matrix tablets loaded with an oppositely charged drug exhibit complex drug-release mechanisms. In this study, the release mechanism of a cationic drug doxazosin mesylate (DM) from matrix tablets based on an anionic polyelectrolyte λ-carrageenan (λ-CARR) is investigated. The drug release rates from λ-CARR matrices are correlated with binding results based on potentiometric measurements using the DM ion-sensitive membrane electrode and with molecular characteristics of the DM-λ-CARR-complex particles through hydrodynamic size measurements. Experiments are performed in solutions with different ionic strength and with the addition of an anionic surfactant sodium dodecyl sulphate (SDS). It is demonstrated that in addition to swelling and erosion of tablets, the release rates depend strongly on cooperative interactions between DM and λ-CARR. Addition of SDS at concentrations below its critical micelle concentration (CMC) slows down the DM release through hydrophobic binding of SDS to the DM-λ-CARR complex. On the contrary, at concentrations above the CMC SDS pulls DM from the complex by forming mixed micelles with it and thus accelerates the release. Results involving SDS show that the concentration of surfactants that are naturally present in gastrointestinal environment may have a great impact on the drug release process.

Design of a Time-Controlled Pulsatile Release System for Propranolol Using the Dry-Coated Method: In Vitro and In Vivo Evaluation.

The objective of this study was to design a time-controlled pulsatile release (TCPR) system containing propranolol (PNH) as an active pharmaceutical ingredient. Here, the developed dosage forms were coated with hydroxypropyl-methylcellulose (HPMC) and other excipients as barrier layer using dry-coated technology. The influence of HPMC, microcrystalline cellulose (MCC), and lactose in the outer coating and the coating weight on drug release were investigated. Then, a three-factor, five-level central composite design (CCD) and response surface method were used to optimize the formula of the coating. After data processing, the optimal prescription was found to be as follows: HPMC E50(X1) 86.2mg, MCC(X2) 43.8mg, and lactose (X3) 21.3mg in the coating. Moreover, the in vitro tests showed that the optimized formulation of TCPR had a lag time of 4h followed by a 4-h drug release. Also, determination of the extent of erosion of the TCPR tablets revealed that the lag time is related to the coating erosion speed. The in vivo test in beagle dogs and comparison of the parameters for the TCPR tablets and reference preparations showed significant differences for Tmax (7.83±0.408 and 2±0.00) and Cmax (185.45±28.561 and 587±45.27ng/ml) but no significant differences in the AUC0-∞ (1757.876±208.832 and 1779.69±229.02ng h/ml). These results demonstrated that the TCPR tablets successfully prolonged the lag time and controlled the release of propranolol.

In Vitro and In Vivo Modeling of Hydroxypropyl Methylcellulose (HPMC) Matrix Tablet Erosion Under Fasting and Postprandial Status

PurposeTo develop a model linking in vitro and in vivo erosion of extended release tablets under fasting and postprandial status.MethodsA nonlinear mixed-effects model was developed from the in vitro erosion profiles of four hydroxypropyl methylcellulose (HPMC) matrix tablets studied under a range of experimental conditions. The model was used to predict in vivo erosion of the HPMC matrix tablets in different locations of the gastrointestinal tract, determined by magnetic marker monitoring. In each gastrointestinal segment the pH was set to physiological values and mechanical stress was estimated in USP2 apparatus rotation speed equivalent.ResultsErosion was best described by a Michaelis–Menten type model. The maximal HPMC release rate (VMAX) was affected by pH, mechanical stress, HPMC and calcium hydrogen phosphate content. The amount of HPMC left at which the release rate is half of VMAX depended on pH and calcium hydrogen phosphate. Mechanical stress was estimated for stomach (39.5 rpm), proximal (93.3 rpm) and distal (31.1 rpm) small intestine and colon (9.99 rpm).ConclusionsThe in silico model accurately predicted the erosion profiles of HPMC matrix tablets under fasting and postprandial status and can be used to facilitate future development of extended release tablets.

Assessment of Tablet Surface Hardness by Laser Ablation and Its Correlation With the Erosion Tendency of Core Tablets

Surface erosion of uncoated tablets results in processing problems such as dusting and defects during coating and is governed by the strength of particle bonding on tablet surface. In this study, the correlation between dusting tendency of tablets in a coating pan with friability and laser ablation surface hardness was assessed using tablets containing different concentrations of magnesium stearate and tartaric acid. Surface erosion propensity of different batches was evaluated by assessing their dusting tendency in the coating pan. In addition, all tablets were analyzed for crushing strength, friability, modified friability test using baffles in the friability apparatus, and weight loss after laser ablation. Tablets with similar crushing strength showed differences in their surface erosion and dusting tendency when rotated in a coating pan. These differences did not correlate well with tablet crushing strength or friability but did show reasonably good correlation with mass loss after laser ablation. These results suggest that tablet surface mass loss by laser ablation can be used as a minipiloting (small-scale) tool to assess tablet surface properties during early stages of drug product development to assess the risk of potential large-scale manufacturing issues.

Investigating the effect of processing parameters on pharmaceutical tablet disintegration using a real-time particle imaging approach

Tablet disintegration is a fundamental parameter that is tested in vitro before a product is released to the market, to give confidence that the tablet will break up in vivo and that active drug will be available for absorption. Variations in tablet properties cause variation in disintegration behaviour. While the standardised pharmacopeial disintegration test can show differences in the speed of disintegration of different tablets, it does not give any mechanistic information about the underlying cause of the difference. With quantifiable disintegration data, and consequently an improved understanding into tablet disintegration, a more knowledge-based approach could be applied to the research and development of future tablet formulations.The aim of the present research was to introduce an alternative method which will enable a better understanding of tablet disintegration using a particle imaging approach. A purpose-built flow cell was employed capable of online observation of tablet disintegration, which can provide information about the changing tablet dimensions and the particles released with time. This additional information can improve the understanding of how different materials and process parameters affect tablet disintegration. Standard USP analysis was also carried out to evaluate and determine whether the flow cell method can suitably differentiate the disintegration behaviour of tablets produced using different processing parameters.Placebo tablets were produced with varying ratios of insoluble and soluble filler (mannitol and MCC, respectively) so that the effect of variation in the formulation can be investigated. To determine the effect of the stress applied during granulation and tableting on tablet disintegration behaviour, analysis was carried out on tablets produced using granular material compressed at 20 or 50bar, where a tableting load of either 15 or 25kN was used. By doing this the tablet disintegration was examined in terms of the tablet porosity by monitoring the tablet area and particle release. It was found that when 20 and 50bar roller compaction pressure was used the USP analysis showed almost identical disintegration times for the consequent tablets. With the flow cell method a greater tablet swelling was observed for the lower pressure followed by steady tablet erosion. Additionally, more particles were released during disintegration due to the smaller granule size distribution within the tablet. When a higher tableting pressure was applied the tablet exhibited a delay in the time taken to reach the maximum swelling area, and slower tablet erosion and particle release were also observed, largely due to the tablet being much denser causing slower water uptake. This was in agreement with the USP analysis data. Overall it was confirmed by using both the standard USP analysis and flow cell method that the tablet porosity affects the tablet disintegration, whereby a more porous tablet disintegrates more slowly. But a more in-depth understanding was obtained using the flow cell method as it was determined that tablets will swell to varying degrees and release particles at different rates depending on the roller compaction and tableting pressure used.

Evaluation of Ocimum basilicum L. seed mucilage as rate controlling matrix for sustained release of propranolol HCl

Polysaccharide mucilage derived from the seeds of Ocimum basilicum L. (family Lamiaceae) was investigated for use in matrix formulations containing propranolol hydrochloride. Basil mucilage was extracted and several tablets were formulated. The effect of mucilage on drug release rate was evaluated in comparison with tablets containing two kinds of hydroxypropyl methylcellulose (HPMC K4M and HPMC K100M) as standard polymer. The release data were fitted to several models for kinetic evaluation. The results showed that hardness decreased and friability of tablets increased as the concentration of mucilage increased. The rate of release of propranolol HCl from O. basilicm mucilage matrices was mainly controlled by the drug: mucilage ratio. Drug release was slower from the HPMC K4M and HPMCK100M containing tablets compared to the mucilage containing matrices than the drug release from matrices containing O. basilicum seed mucilage in similar ratios. Formulations containing O. basilicm mucilage were found to exhibit suitable release pattern. The results of kinetic analysis showed that in tablets containing O. basilicm mucilage the highest correlation coefficient was achieved with the zero order model. The swelling and erosion studies revealed that, as the proportion of mucilage in tablets was increased, there was a corresponding increase in percent swelling and a decrease in percent erosion of tablets.

Inter-Grade and Inter-Batch Variability of Sodium Alginate Used in Alginate-Based Matrix Tablets

The purpose of this study is to characterize the inter-grade and inter-batch variability of sodium alginate used in the formulation of matrix tablets. Four different grades and three batches of one grade of sodium alginate were used to prepare matrix tablets. Swelling, erosion, and drug release tests of sodium alginate matrix tablets were conducted in a USP dissolution apparatus. Substantial differences in swelling and erosion behavior of sodium alginate matrix tablets were evident among different viscosity grades. Even different batches of the same grade exhibit substantial differences in the swelling and erosion behavior of their matrix tablets. The erosion behavior of sodium alginate matrix tablets can be partly explained by their rheological properties (both apparent viscosity and viscoelasticity) in solution. Sodium alginate with higher apparent viscosity and viscoelasticity in solution show slower erosion rate and higher swelling rate. Compacts prepared from grades or batches with higher viscosity and higher viscoelasticity show slower drug release. For grades or batches with similar apparent viscosities, apparent viscosities of sodium alginate solution at low concentration alone are not sufficient to predict the functionality of sodium alginate in matrix tablets. Viscoelastic properties of sodium alginate solutions at one high concentration corresponding to the polymer gel state, may be suitable indicia of the extended release behavior of sodium alginate matrix tablets.

Influence of dissolution media pH and USP1 basket speed on erosion and disintegration characteristics of immediate release metformin hydrochloride tablets

Purpose: To investigate the influence of the pH of the dissolution medium on immediate release 850 mg metformin hydrochloride tablets.Methods: A traditional wet granulation method was used to manufacture metformin hydrochloride tablets with or without a disintegrant. Tablet dissolution was conducted using the USP apparatus I at 100 rpm.Results: In spite of its pH-independent high solubility, metformin hydrochloride tablets dissolved significantly slower in 0.1 N HCl (pH 1.2) and 50 mM pH 4.5 acetate buffer compared with 50 mM pH 6.8 phosphate buffer, the dissolution medium in the USP. Metformin hydrochloride API compressed into a round 1200 mg disk showed a similar trend. When basket rotation speed was increased from 100 to 250 rpm, the dissolution of metformin hydrochloride tablets was similar in all three media. Incorporation of 2% w/w crospovidone in the tablet formulation improved the dissolution although the pH-dependent trend was still evident, but incorporation of 2% w/w croscarmellose sodium resulted in rapid pH-independent tablet dissolution.Conclusion: In absence of a disintegrant in the tablet formulation, the dissolution was governed by the erosion-diffusion process. Even for a highly soluble drug, a super-disintegrant was needed in the formulation to overcome the diffusion layer limitation and change the dissolution mechanism from erosion-diffusion to disintegration.