The Effect of Some Surfactants on the in- Vitro Properties of Double Compressed Tablets

Abstract

The effect of different types and concentrations of some surface active agents as well as the method of surfactant incorporation on the in - vitro properties of aspirin tablets as a model for double compressed tablets was studied. The formulated tablets were evaluated using the U. S. P. official tests and some other selected non-official tests. These tests include: uniformity of weight, uniformity of content, disintegration, dissolution, hardness, friability and thickness. Incorporation of a low concentration (0.2 % w/w) of surface active agents i n the formulation of tablets decreased the disintegration time but did not affect their dissolution rate. Higher concentrations of surface active agents retarded the dissolutiono of tablets. Non ionic surfactants showed higher regarding effect than ionic surfactants. Changing the method of surfactant incorporation did not greatly affect the dissolution rate of tablets.     

A Comparative Evaluation of Some Starches as Disintegrants for Double Compressed Tablets

The effect of different types and concentrations of some starches as disintegrants on the properties of aspirin tablets as a model for double compressed tablets was studied. The formulated tablets were evaluated using the U.S.P. official tests and some other selected nonofficial tests. These tests include: uniformity of weight, uniformity of content, disintegration, dissolution, hardness, friability and thickness. Maize starch was found to be the most suitable disintegrant for the formulation of double compressed tablets while rice starch was the worst disintegrant, in this study, as it significantly increased the hardness of tablets and showed a prolonged disintegration time as well as a poor dissolution rate. increasing the starch content of tablets resulted in a marked increase in their dissolution rate.     

A Comparative Evaluation of Some Starches as Disintegrants for Double Compressed Tablets

Abstract

The effect of different types and concentrations of some starches as disintegrants on the properties of aspirin tablets as a model for double compressed tablets was studied. The formulated tablets were evaluated using the U.S.P. official tests and some other selected nonofficial tests. These tests include: uniformity of weight, uniformity of content, disintegration, dissolution, hardness, friability and thickness. Maize starch was found to be the most suitable disintegrant for the formulation of double compressed tablets while rice starch was the worst disintegrant, in this study, as it significantly increased the hardness of tablets and showed a prolonged disintegration time as well as a poor dissolution rate. increasing the starch content of tablets resulted in a marked increase in their dissolution rate.     

Lubricants as a Formulation Factor Affecting In Vitro Properties of Double Compressed Tablets

Abstract

The effect of some lubricants and their concentrations on the in-vitro properties of aspirin tablets as a model of tablets prepared by double compression was studied. The formulated tablets were evaluated using the U.S.P XX official tests and some other selected non-official tests. These tests include: uniformity of weight, uniformity of content, disintegration, dissolution, hardness, friability and thickness. The obtained results showed that all the prepared formulae fulfilled the requirements of such tests. Talc at a concentration of 3% w/w was found to be the most suitable lubricant for the formulation of aspirin tablets. On the other hand, magnesium stearate was found to be the worst lubricant in this study.     

Effect of Scaling-Up and Formulation Factors on the Qualities of Prednisone Tablets

Four different tablet manufacturing techniques were scaled-up from a bench scale to a semi-large scale in order to study the effect of scaling-up on weight variation and content uniformity of prednisone tablets. One method was further scaled-up to a production scale, and the tablets obtained were tested for content uniformity. The effect of binders and lubricants on tablet hardness, disintegration, dissolution and chemical stability was investigated. It is shown that scaling-up of some techniques affect content uniformity of tablets. The various tablet parameters have been also found to be influenced by the type of binder and lubricant used and by aging of the tablets at normal and accelerated conditions. The presence or absence of intragranular starch as disintegrant appears to affect some of the tablet qualities.     

Modulation of the wettability of excipients by surfactant and its impacts on the disintegration and release of tablets

Objective: To investigate the modulation of the wettability of excipients by different types of surfactants and its impacts on the disintegration of tablets and drug release.

Materials and methods: The critical micelle concentration (CMC) of surfactants, including sodium dodecyl sulfate (SDS), sodium dodecyl benzene sulfonate (SDBS), dodecyl trimethyl ammonium bromide (DTAB), cetyltrimethyl ammonium bromide (CTAB) and polysorbate (Tween-20 and Tween-80), was obtained using the platinum ring method. Contact angles of surfactant solutions on the excipient compacts and double-distilled water on the mixture of surfactant and the other excipient (magnesium stearate (MgSt) or sodium alginate (SA)) were measured by the sessile drop technique. Besides, surface free energy of excipients was calculated by the Owens method. Finally, the disintegration of tablets and in vitro dissolution testing were performed according to the method described in USP.

Results and discussion: The wettability of excipients could be enhanced to different extent with low concentration of surfactant solutions and maintained stable basically after CMC. For MgSt (hydrophobic excipient), the shorter the hydrophobic chain (C₁₂, including SDS and DTAB), the better the wettability with the addition of surfactant in the formulation, leading to the shorter disintegration time of tablets and higher drug release rate. In contrast, the wettability of SA (hydrophilic excipient) was reduced by adding surfactant, resulting in the longer disintegration time of tablets and lower release rate.

Conclusion: The modulation of the wetting of pharmaceutical excipients by surfactant had changed the disintegration time of tablets and drug release rate to a greater extent.     

Role of Surfactant on Drug Release from Tablets

The addition of a surfactanat into a tablet formulation appears to be attractive method of improve the drug release rate. The improved release rate is often associated with the effect of surfactant increasing the hydrophilicity of the dosage form thereby promoting drug dissolution. The findings of this investigation showed tha the presence of surfactant infulenced the tablet disintegration rate, producing a finer dispersion of disintergrated particles. It follows that the action of surfactant improving drug dissolution from tablets may be attributed ot the aciton of surfactnat producing fine disintegrated particles with correspondingly larger surface area for drug dissolution. It was also demonstrated that upon tablet disintergration the disinstegrated particles have a tri-moal frequency distribution.     

Role of Surfactant on Drug Release from Tablets

Abstract

The addition of a surfactanat into a tablet formulation appears to be attractive method of improve the drug release rate. The improved release rate is often associated with the effect of surfactant increasing the hydrophilicity of the dosage form thereby promoting drug dissolution. The findings of this investigation showed tha the presence of surfactant infulenced the tablet disintegration rate, producing a finer dispersion of disintergrated particles. It follows that the action of surfactant improving drug dissolution from tablets may be attributed ot the aciton of surfactnat producing fine disintegrated particles with correspondingly larger surface area for drug dissolution. It was also demonstrated that upon tablet disintergration the disinstegrated particles have a tri-moal frequency distribution.     

Effect of Crospovidone on the Physical Properties of Acetaminophen Tablets

Acetaminophen tablets containing minimum amount of excipients and varying amounts of cross linked polyvinyl pyrrolidone were prepared under accurately controlled conditions of compression speed and pressure. The disintegration time, dissolution rate, crushing force, friability as well as effect of temperature and humidity on these parameters during storage were determined. Increasing proportions of the cross linked polymer (1-10%) did not influence crushing force or friability but significantly decreased disintegration and dissolution time. Satishctory tablets with desired properties were obtained by incorporation of optimum quantity of crospovidone. Storage of acetaminophen tablets at room temperature and humidity for a period of 4 weeks did not alter any of the physical properties tested weekly. However the combined effect of elevated temperature and humidity on tablet properties, especially on the dissolution time was significant. The influence of incorporation of equal amounts of crospovidone intragranularly and intra-plus extragranularly on the properties of granules and tablets were also evaluated with scaled-up formulations.     

Effect of Crospovidone on the Physical Properties of Acetaminophen Tablets

Abstract

Acetaminophen tablets containing minimum amount of excipients and varying amounts of cross linked polyvinyl pyrrolidone were prepared under accurately controlled conditions of compression speed and pressure. The disintegration time, dissolution rate, crushing force, friability as well as effect of temperature and humidity on these parameters during storage were determined. Increasing proportions of the cross linked polymer (1-10%) did not influence crushing force or friability but significantly decreased disintegration and dissolution time. Satishctory tablets with desired properties were obtained by incorporation of optimum quantity of crospovidone. Storage of acetaminophen tablets at room temperature and humidity for a period of 4 weeks did not alter any of the physical properties tested weekly. However the combined effect of elevated temperature and humidity on tablet properties, especially on the dissolution time was significant. The influence of incorporation of equal amounts of crospovidone intragranularly and intra-plus extragranularly on the properties of granules and tablets were also evaluated with scaled-up formulations.     

The Influence of the Rate of Production of Tablets at Constant Pressure Upon Their Physical Properties

Spray dried and granulated lactosa was subjected to sieve analysis, and flow rate together with angle of repose also determined. Tablets of lactose were prepared, at pressures of SO 2 and 120 MN/m at production rates from 1 to BO per minute, using an instrumented single punch tablet machine.

The physical properties of the tablets determined were hardness, thickness, uniformity of weight, friability and disintegration time. They were found to conform to United States Pharmacopoeal standards for uniformity of weight and thickness, friability decreased with tablet hardness.

Examination of tablet surfaces, using a scanning electronmicro-scope, revealed differences in structure related to speed of production with smoother more compact surfaces produced as tabletting rate was increased. This was most pronounced at the highest punch pressure and probably is the result of faster consolidation of particles and their surface fusion. A result of this was that disintegration time for tablets, produced at a given pressure, increased in direct proportion to the speed of production. Repose angles in the range of 24-30 had no significant effect on physical properties of tablets and whatever the rate of production die fill and consequently tablet weight did not vary.

Rate of tablet production can. as shown here, influence their physical properties with those produced at higher rates having increased disintegration tiaws and probably less satisfactory dissolution characteristics.     

Evaluation of Commercial Metronidazole Tablets

Six commercial brands of metronidazole tablets from different manufacturers were elected for this study. The tablets were evaluated using the official and non-official tests of U.S.P. XX. These tests include: uniformity of weight, hardness, friability, disintegration time and dissolution rate. The results obtained showed that most of these brands passed the U.S.P. requirements. The dissolution rate studies showed a great differences in drug release characteristics between brands and also between batches of the same brand. Studies on drug content for each metronidazole brand showed a great variation between the brands and to a less extent within the different batches of the same brand. For the intense bitter taste of metronidazole, a trial was done to prepare it in the form of capsule. The dissolution rate of such capsule was much better than all the commercial tablets studied.     

Evaluation of Commercial Metronidazole Tablets

Abstract

Six commercial brands of metronidazole tablets from different manufacturers were elected for this study. The tablets were evaluated using the official and non-official tests of U.S.P. XX. These tests include: uniformity of weight, hardness, friability, disintegration time and dissolution rate. The results obtained showed that most of these brands passed the U.S.P. requirements. The dissolution rate studies showed a great differences in drug release characteristics between brands and also between batches of the same brand. Studies on drug content for each metronidazole brand showed a great variation between the brands and to a less extent within the different batches of the same brand. For the intense bitter taste of metronidazole, a trial was done to prepare it in the form of capsule. The dissolution rate of such capsule was much better than all the commercial tablets studied.     

Preparation and dissolution characteristics of indomethacin sustained release beads

Indomethacin is a nonsteroidal anti-inflammatory agent and has a short half life, and causes gastric irritation. Sustained release beads of indomethacin were prepared and dissolution profiles were investigated. Beads were prepared by allowing drops of a suspension of the drug and excipients in a solution of cellulose acetate phthalate to drop into an acetic acid solution by means of a peristaltic pump. In a previous study¹, sulfadiazine was used as a model drug to prepare beads by a similar method and the effects of various viscosity agents on the properties of these beads were assessed. Glycerin, polymers (Methocel and Avicel), and surfactants (Tween 80 and Span 80) were used as excipients. The incorporation of various viscosity agents and polymers into the suspension yielded beads with different disintegration and dissolution values. A high performance liquid chromatography method showed no indication of drug degradation during the preparation. The dissolution studies of the indomethacin preparations demonstrated differences in drug release properties depending on composition and method of preparation. The preparation with equal quantities of the two surfactants (Tween 80 and Span 80) released the drug at the slowest rate.     

Kozeny–Carman permeability relationship with disintegration process predicted from early dissolution profiles of immediate release tablets

This study was oriented toward the disintegration profiling of the diclofenac sodium (DS) immediate-release (IR) tablets and development of its relationship with medium permeability k_perm based on Kozeny–Carman equation. Batches (L1–L9) of DS IR tablets with different porosities and specific surface area were prepared at different compression forces and evaluated for porosity, in vitro dissolution and particle-size analysis of the disintegrated mass. The k_perm was calculated from porosities and specific surface area, and disintegration profiles were predicted from the dissolution profiles of IR tablets by stripping/residual method. The disintegration profiles were subjected to exponential regression to find out the respective disintegration equations and rate constants k_d. Batches L1 and L2 showed the fastest disintegration rates as evident from their bi-exponential equations while the rest of the batches L3–L9 exhibited the first order or mono-exponential disintegration kinetics. The 95% confidence interval (CI_95%) revealed significant differences between k_d values of different batches except L4 and L6. Similar results were also spotted for dissolution profiles of IR tablets by similarity (f₂) test. The final relationship between k_d and k_perm was found to be hyperbolic, signifying the initial effect of k_perm on the disintegration rate. The results showed that disintegration profiling is possible because a relationship exists between k_d and k_perm. The later being relatable with porosity and specific surface area can be determined by nondestructive tests.     

Prelimnaky Evaluation of Cissus Root Gum as a Binder in Sodium Salicylate Tablet Formulations

Abstract

Cissus root gum was processed and evaluated as a binder in lactose-based tablets each containing 100 mg of sodium salicylate as the active ingredient. Acacia binder was used as basis for comparison. Tablet hardness, friability, disintegration time and dissolution rate were the parameters investigated. The cissus gum gave hard and non-friable tablets at 1 - 3% w/w concentration of the tablet formula. Tablets containing above 2% w/w of the cissus gum gave high disintegration time values and the pattern of dissolution of the incorporated drug suggests that the gum may be useful in prolonged release tablet formulations. No significant changes in the tablet properties was observed after storage at 30°C for 16 weeks.     

Storage Related Physico-Chemical Changes in Aspirin and Phenylbutazone Tablets Compressed With Different Initial Moisture Content

Abstract

The storage conditions as well as the compressional conditions of the aged tablets were found to have significant effect on their physico-chemical properties. In this study the changes in tablet weight, thickness, hardness, disintegration, drug release and drug content were evaluated for aspirin and phenylbutazone (pbz) tablets made with microcrystalline cellulose (MCC) and lactose bases. Tablets were made with different initial moisture content and stored at 40°C/90% relative humidity (R.H.). Tablet thickness was found, in general, to increase with storage, this increase was more prominent with aspirin. The increase in thickness was always accompanied with a decrease in hardness. There was a marked increase in disintegration time and decrease in dissolution rate of phenylbutazone tablets. This was more significant for the lactose based tablets, while, for aspirin tablets there was a negligible increase in both dissolution rate and the disintegration time. The present study indicated that incorporation of drugs in tablet bases has resulted in a different response towards storage     

Formulation and evaluation of rapidly disintegrating fenoverine tablets: effect of superdisintegrants

The objective of this study was to formulate directly compressible rapidly disintegrating tablets of fenoverine with sufficient mechanical integrity, content uniformity, and acceptable palatability to assist patients of any age group for easy administration. Effect of varying concentrations of different superdisintegrants such as crospovidone, croscarmellose sodium, and sodium starch glycolate on disintegration time was studied. Tablets were evaluated for weight variation, thickness, hardness, friability, taste, drug content, in vitro and in vivo disintegration time, and in vitro drug release. Other parameters such as wetting time, water absorption ratio ('R'), and drug-excipient compatibility were also evaluated. The disintegration time of the best rapidly disintegrating tablet formulation among those tested was observed to be 15.9 sec in vitro and 37.16 sec in vivo. Good correlation was observed between disintegration time and 'R' for each of the three superdisintegrants at the concentrations studied. Considering the 'R' values and disintegration time, crospovidone was significantly superior (p < 0.05) compared to the other superdisintegrants tested. Release of drug was faster from formulations containing 6% crospovidone (CP 6) compared to the marketed fenoverine (Spasmopriv(R)) capsules. Similarity factor 'f(2)' (51.5) between dissolution profiles of the rapidly disintegrating tablet formulation CP 6 and the marketed formulation indicated that the two dissolution profiles were similar. Differential scanning calorimetric studies did not indicate any excipient incompatibility, either during mixing or after compression. In conclusion, directly compressible rapidly disintegrating tablets of fenoverine with lower friability, acceptable taste, and shorter disintegration times were obtained using crospovidone and other excipients at optimum concentrations.     

Crosslinked Starch as Sustained Release Agent

Different types of crosslinked starches and pregelatinized-crosslinked starches were evaluated for their use as hydrophilic matrices. Some fundamental properties of these chemically modified starches, e.g. granule swelling power and viscosity of the dispersion in function of pH and ionic strength, were studied. Dissolution tests and the rate and amount of water uptake were evaluated on tablets containing theophylline and modified starch (40/60 w/w), compressed on an instrumented tablet press at three different pressures (50,200 and 300 MPa.). Theophylline releasing profiles were determined using the paddle system at a rotational speed of 50 rpm Water, simulated gastric fluid, and simulated intestinal fluid were used as dissolution media. Crosslinked starches showed a poor swelling power and dispersion viscosity in comparison to pregelatinized starch and pregelatinized-crosslinked starches. The pregelatinized-crosslinked starches developed less swelling power than the pregelatinized starch, but they showed higher dispersion viscosity than the pregelatinized starch. The viscosity of all starch dispersions was not affected by ionic strength. An alkaline pH dramatically increased the dispersion viscosity of pregelatinized starch and pregelatinized-crosslinked starches. Drug dissolution rate was lower for tablets containing pregelatinized starch than for tablets containing pregelatinized-crosslinked starches. This phenomenon can be related to the rate and amount of water uptake. The dissolution rate seemed not to be influenced by the compression force nor by the composition of the dissolution media. The results indicate that crosslinked starches, either pregelatinized or not, are not suitable as sustained release agents.     

Preparation and dissolution characteristics of indomethacin sustained release beads

Abstract

Indomethacin is a nonsteroidal anti-inflammatory agent and has a short half life, and causes gastric irritation. Sustained release beads of indomethacin were prepared and dissolution profiles were investigated. Beads were prepared by allowing drops of a suspension of the drug and excipients in a solution of cellulose acetate phthalate to drop into an acetic acid solution by means of a peristaltic pump. In a previous study¹, sulfadiazine was used as a model drug to prepare beads by a similar method and the effects of various viscosity agents on the properties of these beads were assessed. Glycerin, polymers (Methocel and Avicel), and surfactants (Tween 80 and Span 80) were used as excipients. The incorporation of various viscosity agents and polymers into the suspension yielded beads with different disintegration and dissolution values. A high performance liquid chromatography method showed no indication of drug degradation during the preparation. The dissolution studies of the indomethacin preparations demonstrated differences in drug release properties depending on composition and method of preparation. The preparation with equal quantities of the two surfactants (Tween 80 and Span 80) released the drug at the slowest rate.