Orally Disintegrating Tablets Using Starch and Fructose - Pharmaceutical Technology

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Orally Disintegrating Tablets Using Starch and Fructose
The authors demonstrated that ODTs can be obtained by direct compression of a mixture of starch, fructose, and SMCC.

Pharmaceutical Technology
pp. 92-99

Materials and methods

Materials . Tate & Lyle Ingredients (Decatur, IL) donated starch and fructose. Microcrystalline cellulose (MCC) was obtained from FMC BioPolymer (Newark, DE). JRS Pharma (Rosenberg, Germany) donated silicified microcrystalline cellulose (SMCC) in three different bulk grades. Based on bulk densities (BD) and average particle sizes (APS) the grades were labeled as SMCC1 with an APS of 60 μm and BD of 0.25–0.37 g/cm3, SMCC2 an APS of 110 μm and BD of 0.25–0.37g/cm3, and SMCC3 an APS of 110 μm and BD of 0.35–0.50g/cm3. Caffeine and sodium phosphate monobasic were obtained from Sigma-Aldrich (St. Louis, MO). Spectrum (Gardena, CA) provided magnesium stearate and talc.

Table I: Composition in percentages of the formulations (F) studied.
Manufacture of tablets. To study the effect of type and concentration of the binder, the authors prepared different formulations containing SMCC1, SMCC2, SMCC3, or MCC, and labeled them as F1 to F12 as shown in Table I. After selection of the most suitable binding agent and the most effective concentration for disintegration, formulations F13 to F17 were used to determine the optimal fast dissolving excipient combination. With the exception of magnesium stearate and talc, all ingredients weighed for a 300-g batch size were sieved through an 850 μm mesh screen. A tumbling mixer was used to blend the ingredients for 20 min at 25 rev/min. Following this initial period of mixing, magnesium stearate (0.5% w/w) and talc (0.5% w/w) were added, and the blend was mixed for an additional 5 min. A Stokes Dual Pressure Press Model 2 (Compression Components & Service, Warminster, PA) fitted with an 1.0-cm flat-faced beveled edged punch and dye set (Natoli Engineering, Saint Charles, MO) was used to tablet each of the prepared formulations into 400 mg tablets. Three tablet batches were prepared per formulation, one in each of three average hardness ranges: low (3.5–4.5 kP), medium (4.6–5.5 kP), and high (5.6–7.0 kP).

Physical testing. To determine weight uniformity of the batches, 10 tablets were weighed and the mean and standard deviation was determined. A VK 200 Tablet Hardness Tester (Varian, Palo Alto, CA) was used to determine the tablet hardness, for the average of 10 tablets. A micrometer was used to measure thickness and diameter of 10 tablets. A friabilator based on the specifications provided in the US Pharmacopeia was used to measure the friability of the tablet batches. The samples consisted of a number of tablets with a combined weight as close to 6.5 g as possible. Tablets were dedusted thoroughly before and after 100 rotations and prior to weighing, by dusting through an 850 μm mesh screen. The friability was obtained from the percentage weight lost due to abrasion and tablet fracture.

Porosity. Percent relative porosity (ε) was obtained using the relationship between apparent density (ρapp) and true density (ρtrue) as shown in Equation 1 (1):

Briefly, the apparent density was calculated from average values for thickness and diameter of 10 tablets. An AccuPyc 1330 Pycnometer (Micromeritics Instrument, Norcross, GA) was used to measure true density. The same tablets used in the apparent density evaluation (n = 10) were placed inside the measurement chamber of the pycnometer, this was purged with helium four times at 20 psi, before average true density determination (n = 3) at the same pressure.

Disintegration test. A USP disintegration test apparatus was used to establish disintegration times in 600 mL phosphate buffer pH 6.8 at 372C. The USP defines the disintegration time as the time required for the last of six tablets to disintegrate. According to the FDA guidance on ODTs, to be classified as an ODT, the last tablet should disintegrate in 30 s or less (3).

Drug-content uniformity. To study the content uniformity of selected tablet batches, the authors determined the caffeine content of 10 tablets. Each tablet was dissolved in 200 mL of phosphate buffer (pH = 6.8) by means of a magnetic stirrer. After total dissolution, a 1-mL sample was filtered through a 10-μm pore size filter, and assayed for caffeine in a μQuant UV-Vis spectrophotometer (BIO-TEK Instruments, Winooski, VT) set at a wavelength of 273 nm. The average drug content and standard deviation were obtained from 10 tablets.

Particle sizing . A Malvern Mastersizer X (Malvern Instruments, Worcestershire, UK) was used to determine the median particle-size distribution of fructose and starch. Powders were dispersed in cyclohexane (refractive index 1.4235) and 10 mL were added to a small-volume dispersion cell before measurement.


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