Optimum Tablet Research Articles

Characterization of Taro (Colocasia esculenta) stolon polysaccharide and evaluation of its potential as a tablet binder in the formulation of matrix tablet

This investigation focuses on the extraction, characterization, and evaluation of taro (Colocasia esculenta) stolon polysaccharide (TSP) as a tablet binding agent, which is obtained from edible taro stolon. TSP was subjected to phytochemical screening and characterized by FTIR, DSC, TGA, DTA, XRD, particle size, polydispersity index, zeta potential, rheological behavior, and SEM. The tablets prepared with varying concentrations of TSP (2.5 %, 5 %, 7.5 %, and 10 % w/w) and diclofenac sodium (DS) were evaluated and compared with the same concentrations of gum acacia and PVP K-30. The presence of carbohydrates was confirmed by Molisch's test. The FTIR spectra established the compatibility of the drug with excipients. The SEM images revealed asymmetric and elongated particles of TSP powder. The hydration kinetics study showed matrix hydration and water penetration velocity within the range of 0.602–0.753 g/g and 0.112–0.189 cm/g.h, respectively. The tablets showed drug release of >75 % at 45 min. The release-exponent value above 0.89 indicated a super case II drug transport combining matrix erosion and diffusion. Optimum tablet hardness and very low friability, even at 2.5 % binder concentration, suggested the potential application of the novel TSP as a tablet binder in the formulation of the tablets.

Characterization of 2-((4-(chloromethyl)benzoyl)oxy)benzoate acid for analgesic tablet dosage form formulation

The 2-((4-(chloromethyl)benzoyl)oxy)benzoic acid (4CH2Cl) is a potential analgesic compound derived from salicylic acid and 4-chloromethyl benzoyl chloride. Characterization required 4CH2Cl for the formulation of tablet dosage forms. This study aims investigate the effect of SSG, PVP-K30, and the combination of SSG*PVP K-30 on the formulation of 4CH2Cl tablets. Additionally, this study aimed to obtain the optimum 4CH2Cl tablet composition. The experiment followed the two-factor simplex lattice design and direct compression method. The analgesic activity of 4CH2Cl in the optimal tablet was investigated using the hot-plate methods. The ANOVA of linear models is acceptable and the polynomial coefficients of quadratic models are similar to those of linear models. The coefficient of the linear model shows that SSG and PVP K-30 increase the Carr index (16.26; 20.61), Hausner ratio (1.19; 1.29), hardness (4.19; 9.39), friability (0.48; 0.67), disintegration time (0.34; 7.50), and drug release (85.29; 97.69). The coefficient of the quadratic model shows that SSG*PVP K-30 increased the Carr index (1.90), Hausner ratio (0.04), hardness (1.88), friability (0.06), and drug release (4.56), and decreased disintegration time (−0.30). SSG and PVP K-30 increased Carr index, Hausner ratio, hardness, friability, disintegration time, and drug release. The combination of SSG*PVP K-30 has the same effect, except that the disintegration time decreased. The optimum tablet formula is 4CH2Cl (300 mg), Ne (75 mg), SSG (33.60 mg), PVP K-30 (22.40 mg), MCC (40 mg), and SDL (up to 800 mg). 4CH2Cl tablets can be a candidate and choice for new analgesic drugs in the future.

MODULATING THE DRUG SOLUBILITY OF ACECLOFENAC BY DESIGN AS SOLID LIPID PARTICLES: IN VITRO/IN VIVO CORRELATION

Objective: The main objective of the study was to enhance the dissolution and hence the oral bioavailability of Aceclofenac (ACF). Methods: ACF was formulated as solid lipid particles (SLPs), which compressed into a tablet form for immediate release purpose and certain formulations were then coated by Eudragit RS100 polymer for sustained release action. SLPs of ACF were prepared by melt fusion method under the optimum conditions, using Compritol ATO 888 (Cr), Precirol ATO 5 (Pr), glyceryl monstearate, polyethylene glycols 4000, and Poloxamer 188 at different ratios SLP formulations were characterized for particle size, flow characteristics. The compressed tablets were identified in term of hardness, friability, content, moisture uptake, and in vitro release. Oral pharmacokinetics of the optimum tablet formulation and marketed tablet as reference were studied in rabbits. Results: SLP of acecloenac (ACF) showed accepted flowing properties, and the dissolution rate of the ACF from tablets was significantly enhanced compared to unprocessed drug. The results showed that about 45.5±2.5% of AC was released within 30 min from F1 while 12.7±4.5% was released from commercial AC tablets. The in vivo studies verified that the Cmax was 1.98±0.29, 2.10±0.33, and 4.83±86 µg/µl for the optimized immediate, sustained formula and commercial tablet, respectively. While the area under the curve from zero time to 24 h for the immediate and sustained release formula was 1.79, and 2.41 fold greater than the marketed formulation. Conclusion: The results showed that solid lipid particles under optimized conditions might be an efficient method for improving the solubility and hence the bioavailability of poorly soluble drugs likes ACF. The proper coating of the formula helps to achieve a convenient release of the drug.

Hydroxypropyl Methylcellulose as Hydrogel Matrix and Citric Acid-Locust Bean Gum as Negative Matrix for Controlled Release Tablet.

Purpose: This study aimed at determining the optimum concentration of hydroxypropyl methylcellulose (HPMC) as hydrogel matrix and citric acid-locust bean gum (CA-LBG) as negative matrix for controlled release tablet formulation. In addition, the study was to determine the effect of CA-LBG and HPMC. CA-LBG accelerates the disintegration of tablets into granules so that the HPMC granule matrix swells immediately and controls drug release. The advantage of this method is that the tablets do not produce large HPMC gel lumps without drug (ghost matrix) but form HPMC gel granules, which can be rapidly degraded after all of the drug is released. Methods : The experiment followed the simplex lattice design to obtain the optimum tablet formula with CA-LBG and HPMC concentrations as optimization factors. Tablet production by the wet granulation method and ketoprofen is the model of the active ingredient. The kinetics of ketoprofen release was studied using several models. Results : Based on the coefficients of each polynomial equation that HPMC and CA-LBG increased the value of angle of repose (29.91:27.87), tap index (18.99:18.77), hardness (13.60:13.32), friability (0.41:0.73), and release of ketoprofen (52.48:99.44). Interaction of HPMC and CA-LBG increased the value of angle of repose (3.25), tap index (5.64), and hardness (2.42). Interaction of HPMC and CA-LBG too decreased the friability value (-1.10) and release of ketoprofen (-26.36). The Higuchi, Korsmeyer-Peppas, and Hixson-Crowell model is the kinetics of eight experimental tablet formulas. Conclusions : The optimum concentrations of HPMC and CA-LBG for controlled release tablets are 32.97 and 17.03%, respectively. HPMC, CA-LBG, and a combination of both affect the physical quality of tablet and tablet mass. CA-LBG is a new excipient candidate that can control drug release from tablets by the matrix disintegration mechanism on the tablet.

Tablet Formulation of 2-((3-(Chloromethyl)benzoyl)oxy)benzoic Acid by Linear and Quadratic Models.

Purpose: This research determines the effect of sodium lauryl sulfate (SLS) as a surfactant, croscarmellose sodium (CS) as a disintegrating agent, and SLS–CS combinations on 2-((3-(chloromethyl)benzoyl)oxy)benzoic acid (3CH2Cl) (log P = 3.73) tablet formulations. In addition, this study aims to determine the optimum of the 3CH2Cl tablet formula. Methods: The tablets are manufactured through direct compression according to the simplex lattice design. The optimal SLS and CS concentration was determined in vitro using linear and quadratic models to achieve better tablet disintegration and dissolution. Results: The same linear and quadratic coefficient profiles of SLS and CS indicate that the combined coefficient of SLS–CS with a quadratic model can be used to predict the effect of the SLS–CS combination. Based on the linear model coefficients, SLS and CS increase the value of flow time (9.35; 7.65), Carr index (26.17; 21.17), hardness (9.84; 7.44), friability (0.38; 0.31), disintegrating time (5.74; 2.62), and drug release (84.28; 58.65). The quadratic model coefficient shows that SLS–CS combinations increase flow time (0.60), Carr index (2.00), hardness (1.00), and disintegrating time (1.04). Meanwhile, they decrease friability (−0.02) and drug release (−9.10). Conclusions: SLS, CS, and SLS–CS combinations affect the quality of tablet mass and tablets. The optimum tablet formula was 3CH2Cl (300 mg), Ne (9.38%), SLS (0.92%), CS (2.33%), MCC (5%), and SDL (ad 800 mg). 3CH2Cl has analgesic activity despite the presence of tablet excipients. The 3CH2Cl tablet is an innovative formulation and a new alternative for future analgesic drugs.

DEVELOPMENT AND EVALUATION OF TASTE MASKED ORO-DISINTEGRATING TABLETS OF ITOPRIDE HCl USING DIFFERENT CO-PROCESSED EXCIPIENTS: PHARMACOKINETICS STUDY ON RABBITS

Objective: This study aimed to mask the bitter taste of itopride HCl using the solid dispersion method by solvent evaporation technique and formulate an oral disintegrating tablet (ODT) by direct compression method using different co-processed excipients. Methods: Nine formulae of solid dispersion were prepared to mask the bitter taste of Itopride HCl using Eudragit EPO® and mannitol at different ratios after compatibility studies using infrared spectroscopy (IR). The prepared formulae were subjected to different physicochemical characterization, in vivo taste evaluation, and drug content. The best-selected formulae were used to formulate 10 different ODTs. The prepared tablets were evaluated through hardness, drug content, in vivo-in vitro disintegration, IR, wetting time, and finally, dissolution studies. The selected formula was subjected to a pharmacokinetic study compared to the brand. Results: F5, drug: Eudragit EPO® (1:2) and F8, Drug: Mannitol: Eudragit EPO® (1:1:2) formulae were selected as the best taste-masked formulae based on in vivo taste evaluation, which were used to formulate ten ODTs. The dissolution rate for the prepared ODTs was rapid if compared with the ordinary oral tablets. Statistical significance was obtained using one-way ANOVA among ODT formulae. The optimum tablet Prosolv SMCC 90® based formula (T10) had friability 0.15, wetting time 4±0.35 sec, in vitro dissolution 100.08±0.028% just after 2 min, where the in vitro disintegration time and in vivo disintegration time were 4±0.12 sec and 12±0.049 sec respectively. The relative bioavailability of ODT containing Prosolv SMCC 90®was increased significantly compared to the brand. Conclusion: The obtained results successfully confirmed the potential of the promising Prosolv SMCC 90® based formula (T10) to produce rapid onset action and in-time drug release instead of ordinary tablets containing itopride HCl and that provide by-passing the excessive degradation of drug by first-pass metabolism increasing the oral bioavailability from 60% of marketed drug Ganaton® to 88% for the prepared ODT (T10).

Tablet Formula Optimization From Helminthostachys Zaylanica Extract Using A Simplex Lattice Design

Helminthostachys zeylanica extract has pharmacological activities such as antioxidant, antiinflamatory, and antihyerucemia. This extract is nontoxic substance from the acute and subchronic toxicity tests. This extract has a potency to be formulated into tablet dosage forms. This study aims to optimize a tablet formula from Helminthostachys zeylanica extract. Disintegrant and binder concentrations were independent variables, while physical properties and dissolution time of the tablets were dependent variables. The tablet was prepared by a wet granulation method. Formula was optimized by Simplex Lattice Design. Physicochemical propertiesof granule, physical properties and dissolution of tablet were then analyzed with One Way ANOVA (p = 0.05). Based on granule analysis, specification of physicochemical parameters, such as hausner’s ratio, compressibility index, flowability, repose angle, and water content, met standard British Pharmacopeia. In addition, the starch and PVA concentrations influenced thickness, weight variation, hardness, friability, disintegration time and dissolution of the tablets (p <0.05), except for friability (p> 0.05). Based on this study, the starch and PVA concentrations for the optimum tablet formula were 19.5% and 1.05%, respectively.

DISSOLUTION ENHANCEMENT AND FORMULATION OF FILM COATED TABLETS OF LORNOXICAM BY PHASE TRANSITION METHOD: IN VITRO AND IN VIVO EVALUATION

Objective: This study aimed to enhance the oral solubility and dissolution of poorly soluble lornoxicam by anti-solvent precipitation, and the manufacture of oral tablets by the phase transition method. 
 Methods: The solvent was mixture of polyethylene glycol 400 and absolute ethanol. Three stabilizers Inutec SP1, Pluronic F127, Sucrose ester S1670 at two concentrations and two matrix formers Mannitol, and Avicel PH102 were used to obtain 12 formulae. The formulae were characterized regarding their infrared spectroscopy (IR), differential scanning calorimetry (DSC), particle size (PS) measurement, drug content and dissolution. Further characterizations were done for the optimum formula by scanning electron microscopy (SEM) and X-ray diffraction (XRD). Four tablet formulae were manufactured by phase transition method. The optimum tablets (T3) were evaluated through hardness, drug content, disintegration, dissolution, IR, and stability studies. Finally, (T3) was compared to conventional tablets in New Zealand rabbits using crossover design.
 Results: The dissolution rate for the prepared formulae was enhanced, from 3.44 to 5.96 folds. Statistical significance was obtained using one and two way ANOVA among formulae. The optimum tablet formula (T3) had hardness 5.637±1.57 kg, drug content 90.424±1.19%, disintegration time 341.5±9.62 s and the drug dissolved 72.107±0.0025%. Stability, after one month storage of the selected tablets at (25 °c/60% relative humidity), was satisfactory. The absorption extent of lornoxicam from (T3) compared to the conventional tablets was higher.
 Conclusion: Taken together, the obtained results confirmed successfully the potential of the promising formula (T3), over the conventional tablets of lornoxicam.

Febuxostat loaded β-cyclodextrin based nanosponge tablet: an in vitro and in vivo evaluation

Febuxostat is non-purine, selective inhibitor of xanthine oxidase for treatment of gout. It exhibits poor bioavailability. The goal of the present study was to enhance the oral bioavailability of Febuxostat through β-Cyclodextrin nanosponges, subsequently reduce the dose and side effects. Nanosponges were formed by cross-linking β-Cyclodextrin with carbonate bonds using different molar ratio (1:4, 1:6, 1:8 and 1:10 β-Cyclodextrin: crosslinker). Drug was incorporated by solvent evaporation method. Nanosponge formulations were evaluated and formulations that released (≥ 30%) at first hour followed by controlling the release (≥ 75%) at 6 h were further evaluated and tableted by direct compression. The optimum tablet formulations based upon drug release were investigated for accelerated stability testing and for comparative bioavailability with a marketed product. SEM illustrates porous and sponge like structure. DSC and FTIR studies confirmed the formation of nanosponges and encapsulation of Febuxostat within it. The zeta-potentials were high (− 21.5 to − 32.3 mV). The particle sizes were between 224.7 and 305.6 nm. The in vitro release study showed a biphasic release pattern. Oral bioavailability of selected formulation and marketed product showed enhanced Cmax (1655.0 ± 18.5 vs. 1592.7 ± 95.9 ng/mL) and AUC0−∞ (14,576.7 ± 1681.7 vs. 6449.7 ± 677.1 ng h/mL). The relative bioavailability was found to be 217.9%. Nanosponges is a feasible approach to improve the oral bioavailability of Febuxostat.

Selection of a round convex tablet shape that mitigates the risk of chipping and capping based on systematic evaluation by utilizing multivariate analysis

Selecting a tablet shape that minimizes the risk of chipping and capping during manufacture is important in pharmaceutical industry. Here, the selection was performed based on systematic evaluation for the first time. Abrasion and stress relaxation time were utilized as indices of the occurrences of chipping and capping, respectively. Partial least square regression models that used tablet shape parameters to estimate the tablet's abrasion and stress relaxation time were utilized to develop response surface plots of the effect of the tablet shapes on the occurrence of chipping and capping systematically, and to identify an optimum tablet shape that is expected to have a low occurrence of chipping and capping. A verification study using commercial scale facilities proved that the optimum tablet shape had a lower occurrence of chipping and capping compared to suboptimum examples as speculated by their abrasion and stress relaxation time. The observed mathematical relationship between the tablet shapes and the occurrence of chipping and capping were consistent with the previous studies based on the comparison of limited number of tablet shapes using different formulations. Consequently, it is expected to be applicable to other formulations beyond the evaluated formulation in the present study.

Optimization Formula Tablet Extract of Bengkuang (Pachyrrhizus erosus) Variation Avicel® Ph 101 and Crospovidone

Bengkuang (Pachyrrhizus erosus) contains daidzein which is pro-estrogenic compound, suppressing bone restoration by directing mechanism in bone estrogen receptor. Bengkuang can be developed into a useful source of phytoestrogens as a supplement in menopausal women. This study aims to determine the stability and influence of Avicel® PH 101 and crospovidone on granular flow properties and physical properties of Bengkuang tuber extract. Bengkuang tuber extracts were made into tablet preparations by wet granulation method. Variation of crospovidone composition was between 2-5%, while Avicel® PH 101 was between 38.86 to 41.86%. The tablet formulation is optimized using the Simplex Lattice Design method. The results show that the addition of Avicel® PH 101 can improve the index of determination, water absorption, moisture content, hardness, time of disintegration, and friability of the tablet, as well as crospovidone addition. Avicel® PH 101 and crospovidone interactions increase water content, decrease hardness, and tablet friability. The optimum tablet formula consists of composition of 293 mg of Avicel® PH 101 and 14 mg of crospovidone per tablet. Testing of optimum formula results with SLD method did not differ significantly to the response of the compression index, hardness and friability of the tablet. The tablet was stable at room temperature (30ºC ± 2 ºC) for four weeks.

The Use of D-Optimal Mixture Design in Optimizing Development of Okara Tablet Formulation as a Dietary Supplement.

The usage of soy is increasing year by year. It increases the problem of financial crisis due to the limited sources of soybeans. Therefore, production of oral tablets containing the nutritious leftover of soymilk production, called okara, as the main ingredient was investigated. The okara tablets were produced using the direct compression method. The percentage of okara, guar gum, microcrystalline cellulose (Avicel PH-101), and maltodextrin influenced tablets' hardness and friability which are analyzed using a D-optimal mixture design. Composition of Avicel PH-101 had positive effects for both hardness and friability tests of the tablets. Maltodextrin and okara composition had a significant positive effect on tablets' hardness, but not on percentage of friability of tablets. However, guar gum had a negative effect on both physical tests. The optimum tablet formulation was obtained: 47.0% of okara, 2.0% of guar gum, 35.0% of Avicel PH-101, and 14.0% of maltodextrin.

Development, Characterization and Permeability Assessment Based on Caco-2 Monolayers of Self-Microemulsifying Floating Tablets of Tetrahydrocurcumin

Novel self-microemulsifying floating tablets were developed to enhance the dissolution and oral absorption of the poorly water-soluble tetrahydrocurcumin (THC). Their physicochemical properties and THC permeability across Caco-2 cell monolayers were assessed. The self-microemulsifying liquid containing THC was adsorbed onto colloidal silicon dioxide, mixed with HPMC, gas-generating agents (sodium bicarbonate and tartaric acid), lactose and silicified-microcrystalline cellulose and transformed into tablets by direct compression. The use of different types/concentrations of HPMC and sodium bicarbonate in tablet formulations had different effects on the floating characteristics and in vitro THC release. The optimum tablet formulation (F2) provided a short floating lag time (∼23 s) together with a prolonged buoyancy (>12 h). About 72% of THC was released in 12 h with an emulsion droplet size in aqueous media of 33.9±1.0 nm while that of a self-microemulsifying liquid was 29.9±0.3 nm. The tablet formulation was stable under intermediate and accelerated storage conditions for up to 6 months. The THC released from the self-microemulsifying liquid and tablet formulations provided an approximately three- to fivefold greater permeability across the Caco-2 cell monolayers than the unformulated THC and indicated an enhanced absorption of THC by the formulations. The self-microemulsifying floating tablet could provide a dosage form with the potential to improve the oral bioavailability of THC and other hydrophobic compounds.

The Effect of Powder Properties of Extracts of Herbal Plant and Additives in the Formulation of Herbal Plant Tablets

The compacting properties of powdered herbal plant, Pellodendron Bark (Obaku) to prepare themore convenient dosage form, tablet, than the usual commercial product. The tablet hardness was highly dependent on the particle size of the powdered harbal plant. Formulating some disintegrant such as calcium carboxymethyl cellulose effectively improved the disintegration property of resultant tablet. However, the tablet hardness was decreased by formulating the disintegrant powder. Adding a small amount of fine silica particles in the formulation increased the tablet hardness. The spray-dried extract powder and crude plant powder of Pellodendron Bark showed the different tendency in designing the optimum tablet formulation in the point of hardness and disintegration property. By measuring the compacting properties of the powder formulations, it was suggested that change in plastic property of the powder bed was not the main reason to improve the compacting property of the formulation.

Formulation and Optimization of the Seed Extracts of <i>Glinus lotoides</i> L. Tablets Using Surface Response Method

Tablets of the seed extracts of Glinus lotoides L. were prepared by direct compression using microcrystalline cellulose (MCC). A two-factor-two-level factorial was designed to investigate the combined effects on formulation variable (amount of MCC) and processing variable [compression force (CF)] on tablet properties; crushing strength (H), friability (Fr), and disintegration time (DT). From the results of multiple linear regression analysis, surface responses and contour plots were generated that demonstrated the effects of the independent variables on H, Fr and DT. The optimum combinations of the amount of MCC and CF were obtained by superimposing the contour diagram of tablet\'s H, Fr and DT. The resulting tablets were evaluated for hardness, Fr and DT. The optimum formulation of the tablets composed of the active crude extracts (348 mg), MCC (174 mg), Ac-Di-Sol® (26 mg), and talc (26 mg) were compressed approximately at 12 KN. H, Fr, and DT of the tablets consisting of the optimum formulation were 162 + 6.023N, 0.123% and 13.00 + 0.45 min, respectively. Keywords: Glinus lotoides, optimum tablet formulation, direct compression, surface response, contour plot Ethiopian Pharmaceutical Journal Vol. 24 (2) 2006: pp. 75-83

Methods of Polymer Film Formation and Testing for Obtaining Optimum Tablet Coatings

Methods of Polymer Film Formation and Testing for Obtaining Optimum Tablet Coatings

Fast dispersible ibuprofen tablets

Fast dispersible tablets disintegrate either rapidly in water, to form a stabilized suspension, or disperse instantaneously in the mouth to be swallowed without the aid of water. A direct compression method was used to prepare these two types of tablets containing coated ibuprofen as a high dosed model drug. The properties of the water dispersible tablet, such as porosity, hardness, disintegration time and increase in viscosity after dispersion, were investigated. The selected tablet formulation, containing 26% galactomannan and 5% crospovidone, disintegrates before the galactomannan starts to swell. These tablets disperse in water within 40 s and show a crushing strength of 95 N. To develop an orodispersible tablet, a rotatable central composite design was applied to predict the effects of the quantitative factors mannitol and crospovidone as well as compression force on the characteristics of the tablet. Special emphasis was paid to the development of a wetting test, replacing the normal disintegration method. An optimum tablet formulation, containing 34% mannitol and 13% crospovidone, provides a short wetting time of 17 s and a sufficient crushing strength of 40 N. In conclusion, fast dispersible tablets with acceptable hardness and desirable taste could be prepared within the optimum region.

Optimization of an effervescent tablet formulation using a central composite design optimization of an effervescent tablet formulation containing spray dried l-leucine and polyethylene glycol 6000 as lubricants using a central composite design

A rotatable central composite design is used to evaluate the effects of lubricants and compression force on the physical characteristics of effervescent tablets. Effervescent tablets lubricated with a combination of spray dried l-leucine and polyethylene glycol 6000 are prepared by direct compression and examined. Residual force, crushing strength and disintegration time are considered as response variables and related to the l-leucine and polyethylene glycol concentrations and to the compression force. The calculated models are used to assess the influence of the production factors on tablet properties. As increasing amounts of l-leucine, showing good lubricating properties, reduce the crushing strength and prolong tablet disintegration, the l-leucine concentration is kept at a low level. An optimum tablet formulation contains 2% l-leucine and 3% polyethylene glycol 6000. The tablets have a tensile strength of 0.47 MPa and disintegrate in less than 2 min. Predicted and experimental results are in agreement within a 95% CI.