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.     

Formulation of Griseofulvin Tablets

Abstract

Difficulties in the formulation of griseofulvin tablets are reviewed. A number of griseofulvin direct compression, pre-compression and polyvinylpyrrolidone granulated tablet formulation have been successfully produced and evaluated, in all cases a mixture of dicalcium phosphate dihydrate and calcium phosphato-carbonate complex was used as tablet matrix. Attempts to use other direct compression tablet matrices proved unsuccessful. The tablets produced have been compared with two commercially available products and the data obtained indicated that the formulations developed in this study have potential for further exploitation.     

Effect of the Formulation Parameters on the Characteristics of Pellets

Abstract

Pelletization is increasingly applied currently for the preparation of solid oral controlled-release dosage forms. The production of the particles, which are regular in shape and size, can be achieved with the application of the proper polymer auxiliary materials and new pharmaceutical technological methods (extrusion, spheronization). Regularity in shape and size, attained by the optimization of several production parameters, can promote the coating procedure. Under optimal conditions, particles were prepared for coating in a high-shear mixer, which is used to produce uniform particles. The effect of the rotating speed of the applied chopper and the amount of microcrystalline cellulose in the composition on the physical characteristics of the pellets was modeled by a second-order polynomial equation fitted to the data gathered by a face-centered central composite statistical design.     

The Influence of Formulation on the Dissolution Profile of Diclofenac Sodium Tablets

ABSTRACT

In attempts to design delayed-release tablets of diclofenac sodium, seven experimental batches were produced. The influence of super-disintegrant croscarmellose sodium (CCS), the granulation process, and the thickness of Eudragit® L 100 coating film were evaluated. The values of dissolution efficiency and the similarity factor were used to compare the dissolution profiles of each experimental batch and the reference Voltaren®. Both methods appear to be applicable and useful in comparing dissolution profiles. Based on such values four batches were considered similar when contrasted with the reference. The results suggest an optimal relationship between the amount of CCS and the thickness of the coating film, which provides appropriate dissolution rate of diclofenac sodium from the dosage forms.     

Effect of Formulation and Process Variables on the Dissolution Profile of Naproxen Sodium from Tablets

Abstract

Results of this investigation revealed some important formulation characteristics of naproxen sodium. Tablets made from the granules, prepared by wet granulation method using water, showed a significant decrease in solution as compared to those made by dry blending method. During wet granulation, heat was evolved due to the hydration of naproxen sodium resulting in the retardation of dissolution. The pseudo-polymorphism and hydration is being investigated by Bansal et. al. (1). In addition, when polyvinyl pyrolidone (PVP K-90) was used instead of PVP K-30, the dissolution was further retarted. Addition of cross carmellose sodium (Ac-Di-Sol) did not change the dissolution behavior of these tablets. When naproxen sodium was granulated with water, a decrease in dissolution rate was observed as mixing time was increased from 5 minutes to 15 minutes. The increase in hardness of the tablet from 10 Kp to 18Kp did not alter the dissolution profile of naproxen sodium. When granulation was prepared using a low shear mixer (Planetary mixer) versus a high shear mixer (T.K. Fielder), the resultant tablets exhibited similar dissolution and physical chemical properties.     

Effect of Formulation and Process Variables on the Dissolution Profile of Naproxen Sodium from Tablets

Results of this investigation revealed some important formulation characteristics of naproxen sodium. Tablets made from the granules, prepared by wet granulation method using water, showed a significant decrease in solution as compared to those made by dry blending method. During wet granulation, heat was evolved due to the hydration of naproxen sodium resulting in the retardation of dissolution. The pseudo-polymorphism and hydration is being investigated by Bansal et. al. (1). In addition, when polyvinyl pyrolidone (PVP K-90) was used instead of PVP K-30, the dissolution was further retarted. Addition of cross carmellose sodium (Ac-Di-Sol) did not change the dissolution behavior of these tablets. When naproxen sodium was granulated with water, a decrease in dissolution rate was observed as mixing time was increased from 5 minutes to 15 minutes. The increase in hardness of the tablet from 10 Kp to 18Kp did not alter the dissolution profile of naproxen sodium. When granulation was prepared using a low shear mixer (Planetary mixer) versus a high shear mixer (T.K. Fielder), the resultant tablets exhibited similar dissolution and physical chemical properties.     

Effect of Formulation Composition on the Properties of Controlled Release Tablets Prepared by Roller Compaction

This study discusses the effect of formulation composition on the physical characteristics and drug release behavior of controlled‐release formulations made by roller compaction. The authors used mixture experimental design to study the effect of formulation components using diclofenac sodium as the model drug substance and varying relative amounts of microcrystalline cellulose (Avicel), hydroxypropyl methylcellulose (HPMC), and glyceryl behenate (Compritol). Dissolution studies revealed very little variability in drug release. The t₇₀ values for the 13 formulations were found to vary between 260 and 550 min. A reduced cubic model was found to best fit the t₇₀ data and gave an adjusted r‐square of 0.9406. Each of the linear terms, the interaction terms between Compritol and Avicel and between all three of the tested factors were found to be significant. The longest release times were observed for formulations having higher concentrations of HPMC or Compritol. Tablets with higher concentrations of Avicel showed reduced ability to retard the release of the drug from the tablet matrix. Crushing strength showed systematic dependence on the formulation factors and could be modeled using a reduced quadratic model. The crushing strength values were highest at high concentrations of Avicel, while tablets with a high level of Compritol showed the lowest values. A predicted optimum formulation was derived by a numerical, multiresponse optimization technique. The validity of the model for predicting physical attributes of the product was also verified by experiment. The observed responses from the calculated optimum formulation were in very close agreement with values predicted by the model. The utility of a mixture experimental design for selecting formulation components of a roller compacted product was demonstrated. These simple statistical tools can allow a formulator to rationally select levels of various components in a formulation, improve the quality of products, and develop more robust processes.     

The Effects of Formulation Factors on the Moist Granulation Technique for Controlled-Release Tablets

Controlled-release tablets were prepared by the moist granulation technique (MGT), a granulating method that uses very limited amounts of liquid and requires microcrystalline cellulose (MCC) to absorb moisture. Acetaminophen (APAP) was the model drug, and the polymer hydroxypropylcellulose (HPC) served as the controlled-release agent. The effects of varying drug, binder (polyvinylpyrrolidone, PVP), polymer, and MCC levels on granule properties and tablet dissolution were studied. Dissolution testing was carried out in distilled water using the USP paddle method. In all cases, the granules flowed and compressed well. The granule properties were evaluated by calculating the mean particle size for all batches from sieve analysis data. The results indicate that MGT can be applied to control drug release, and at a polymer content of 44.6% or more, the process is robust enough to allow slight variations in formulation factors without affecting drug release.     

The Effects of Formulation Factors on the Moist Granulation Technique for Controlled-Release Tablets

Controlled-release tablets were prepared by the moist granulation technique (MGT), a granulating method that uses very limited amounts of liquid and requires microcrystalline cellulose (MCC) to absorb moisture. Acetaminophen (APAP) was the model drug, and the polymer hydroxypropylcellulose (HPC) served as the controlled-release agent. The effects of varying drug, binder (polyvinylpyrrolidone, PVP), polymer, and MCC levels on granule properties and tablet dissolution were studied. Dissolution testing was carried out in distilled water using the USP paddle method. In all cases, the granules flowed and compressed well. The granule properties were evaluated by calculating the mean particle size for all batches from sieve analysis data. The results indicate that MGT can be applied to control drug release, and at a polymer content of 44.6% or more, the process is robust enough to allow slight variations in formulation factors without affecting drug release.     

Formulation of Nitrofurantoin Tablets Fulfilling the Pharmacopoeial Specifications

Abstract

The USP XXII specifies that the disintegration time for nitrofurantoin tablets must be not less than 30 minutes, not less than 25% of the drug is dissolved in 60 minutes and not less than 85% is dissolved in 120 minutes. These specifications were done to minimize the side effects and to achieve a proper bioavailability for the drug.

On testing the market tablet preparation (Furadantin), it was found that it does not fit to the [JSP specifications, Nine nitrofurantoin tablet formulations were then tried and each was studied for disintegration time and % dissolution in the first and second hours. The best formula was found to be consisted of adding 2% of collodion in 40% of the starting granules, coated with 4% CAP and adding another 2% of collodion to the remaining 60% of the granules.     

Formulation of Nitrofurantoin Tablets Fulfilling the Pharmacopoeial Specifications

The USP XXII specifies that the disintegration time for nitrofurantoin tablets must be not less than 30 minutes, not less than 25% of the drug is dissolved in 60 minutes and not less than 85% is dissolved in 120 minutes. These specifications were done to minimize the side effects and to achieve a proper bioavailability for the drug.

On testing the market tablet preparation (Furadantin), it was found that it does not fit to the [JSP specifications, Nine nitrofurantoin tablet formulations were then tried and each was studied for disintegration time and % dissolution in the first and second hours. The best formula was found to be consisted of adding 2% of collodion in 40% of the starting granules, coated with 4% CAP and adding another 2% of collodion to the remaining 60% of the granules.     

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®) capsules. Similarity factor ‘f₂’ (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.     

Formulation Studies of Furosemide-Amiloride HCI Combination Tablets

Abstract

During the formulation studies of a furosemide-amiloride HCl combination tablet, an unexpected interaction between the two drugs was encountered. The drugs tended to form aggregates when in contact with the dissolution medium during dissolution testing. This phenomenon decreased the dissolution of both actives significantly. Various formulas were tried to eliminate this problem. Granulation of the formulation with povidone produced a tablet with good dissolution properties. A possible mechanism for preventing the formation of furosemide-amiloride HCl aggregates in the presence of povidone is described.     

Effect of Formulation Variables on Dissolution Profile of Diclofenac Sodium from Ethyl- and Hydroxypropylmethyl Cellulose Tablets

The effects of formulation variables on the release profile of diclofenac sodium from ethyl cellulose (EC) and hydroxypropylmethyl cellulose (HPMC) matrix tablets were investigated. With increase in viscosity of ethyl cellulose used in nonaqueous granulation, a decrease in drug release from the tablets was observed, while the percentage of fines articles passed through 60 mesh) in the granulation had a significant effect on the dissolution profile. Granules containing 15% fines exhibited slow release of the drug in comparison to those containing 30% fines with EC matrices. An analysis of kinetics of drug release from hydrophobic EC matrix showed Fickian diffusion regulated dissolution. Drug release from HPMC tablets followed an apparent zero-order kinetics.     

Effect of Formulation Variables on Dissolution Profile of Diclofenac Sodium from Ethyl- and Hydroxypropylmethyl Cellulose Tablets

Abstract

The effects of formulation variables on the release profile of diclofenac sodium from ethyl cellulose (EC) and hydroxypropylmethyl cellulose (HPMC) matrix tablets were investigated. With increase in viscosity of ethyl cellulose used in nonaqueous granulation, a decrease in drug release from the tablets was observed, while the percentage of fines articles passed through 60 mesh) in the granulation had a significant effect on the dissolution profile. Granules containing 15% fines exhibited slow release of the drug in comparison to those containing 30% fines with EC matrices. An analysis of kinetics of drug release from hydrophobic EC matrix showed Fickian diffusion regulated dissolution. Drug release from HPMC tablets followed an apparent zero-order kinetics.     

Effect of Stearic Acid Particle Size on Surface Characteristics of Film-Coated Tablets

Abstract

Raw material specifications are vital for many excipients used in the manufacture of tablets. Stearic acid powder is widely used in the pharmaceutical industry as a tablet lubricant. This study shows that the variation in particle size of stearic acid not only affects die wall lubrication properties (ejection force) but also affects surface characteristics of film-coated tablets. A coarser grade of stearic acid can dislodge from tablet surfaces during the film-coating process leaving pit marks, whereas a finer grade of stearic acid (less than 100 mesh) results in film-coated tablets having very smooth surfaces. The mechanism of pitting on the tablet surface is described. A specification for stearic acid particle size to overcome this problem is suggested.     

Effect of Stearic Acid Particle Size on Surface Characteristics of Film-Coated Tablets

Raw material specifications are vital for many excipients used in the manufacture of tablets. Stearic acid powder is widely used in the pharmaceutical industry as a tablet lubricant. This study shows that the variation in particle size of stearic acid not only affects die wall lubrication properties (ejection force) but also affects surface characteristics of film-coated tablets. A coarser grade of stearic acid can dislodge from tablet surfaces during the film-coating process leaving pit marks, whereas a finer grade of stearic acid (less than 100 mesh) results in film-coated tablets having very smooth surfaces. The mechanism of pitting on the tablet surface is described. A specification for stearic acid particle size to overcome this problem is suggested.     

Fast-Disintegrating Sublingual Epinephrine Tablets: Effect of Tablet Dimensions on Tablet Characteristics

ABSTRACT

The purpose of this study was to evaluate the effect of changing dimensions on the hardness (H), disintegration time (DT), and wetting time (WT) of fast-disintegrating epinephrine tablets for sublingual administration as potential first aid treatment for anaphylaxis. Tablet formulations I and II, containing 0% and 10% epinephrine bitartrate, respectively, and weighing 150 mg were prepared by direct compression. Formulations were compressed at a range of forces using an 8/32″ die with concave punches (CP); a 10/32″ and an 11/32″ die with CP and flat punches (FP). Tablet weight variation, content uniformity, thickness, H, DT, and WT were measured. The 8/32″, 10/32″, and 11/32″ dies resulted in tablet thickness of ranges 0.25–0.19″, 0.17–0.1″, and 0.16–0.08″, respectively. The DT and WT using the 8/32″ die were ≤10 and ≤30 sec, respectively, at H ≤5.4 ± 0.2 kg for formulation I, and H ≤5.4 ± 0.3 kg for formulation II. The DT and WT were ≤10 and ≤30 sec, respectively, using 10/32″ die/CP, 10/32″ die/FP, 11/32″ die/CP, and 11/32″ die/FP at H ≤6.2 ± 0.6 kg, ≤6.8 ± 0.4 kg, ≤4.9 ± 0.1 kg, and ≤7.2 ± 0.3 kg, respectively, for formulation I. For formulation II, the DT and WT were ≤10 sec and ≤30 sec, respectively, when H < 4 kg. No difference in DT and WT was observed between concave and flat tablets. The 11/32″ and 10/32″ dies resulted in more ideal tablet dimensions for sublingual administration, but H must be maintained <4 kg to ensure rapid DT and WT.     

Effect of Various Polymers on Formulation of Controlled Release (CR) Ibuprofen Tablets by Fluid Bed Technique

The need for controlled release (CR) formulations of ibuprofen tablet, is well recognized. Some such formulations have been marketed but in general only patented.

The purpose of this study was to develop an air suspension method, using a laboratory scale fluidized bed drier to coat the ibuprofen granules. Different polymers including, Eudragits L100, S100, RL100, RS100, L100+S100 (1:1), RL100+RS100 (1:1), ethyl cellulose (EC) and Eudragit RS100+EC (1:1) were utilized. The drug release medium consisted of buffer pH 1.2 for 1st 2h, buffer pH 4.5 for 2nd 2h and buffer pH 7.5 for remaining period of time in all experiments, but the release behaviour of the drug from some formulations was also studied using distilled water. Of the polymers investigated, Eudragit RS100, EC, Eudragit S100 and Eudragit RS100+EC (1:1) exhibited proper release characteristics when used as coating materials. The release patterns were analyzed from the standpoint of diffusion-controlled processes and as first-order kinetics.     

Effect of Various Polymers on Formulation of Controlled Release (CR) Ibuprofen Tablets by Fluid Bed Technique

Abstract

The need for controlled release (CR) formulations of ibuprofen tablet, is well recognized. Some such formulations have been marketed but in general only patented.

The purpose of this study was to develop an air suspension method, using a laboratory scale fluidized bed drier to coat the ibuprofen granules. Different polymers including, Eudragits L100, S100, RL100, RS100, L100+S100 (1:1), RL100+RS100 (1:1), ethyl cellulose (EC) and Eudragit RS100+EC (1:1) were utilized. The drug release medium consisted of buffer pH 1.2 for 1st 2h, buffer pH 4.5 for 2nd 2h and buffer pH 7.5 for remaining period of time in all experiments, but the release behaviour of the drug from some formulations was also studied using distilled water. Of the polymers investigated, Eudragit RS100, EC, Eudragit S100 and Eudragit RS100+EC (1:1) exhibited proper release characteristics when used as coating materials. The release patterns were analyzed from the standpoint of diffusion-controlled processes and as first-order kinetics.