Capsules filling

Flavor characterization Flavor compounding Flavor enhancer Flavor-filled capsules Flavoring agent Flavoring agents... 

Spot welding was once commonly used to lock the cap and body sections of bead-filled capsules together. In the thermal method, two hot metal jaws are brought into contact with the area where the cap overlaps the filled body [23]. 

Replacement of caps and ejection of filled capsules The cap and body bushing portions are rejoined. Pins are used to push the filled bodies up into the caps for closure and to push the closed capsules out of the bushings. Compressed air also may be used to eject the capsules. 

Most capsules are filled on piston-tamp machines. These are fully automatic fillers in which pistons or tamping pins lightly compress the individual doses of powders into plugs (sometimes referred to as slugs ) and eject the plugs into the empty capsule bodies. The compression forces are low, often in the range of 50 200 N, or about 50-100-fold less than typical tablet compression forces. Hence, the plugs frequently will have the consistency of very soft compacts and will not be able to be recovered intact from the filled capsule. 

F Podczeck. The development of an instrumented tamp-filling capsule machine I. Instrumentation of a Bosch GKF 400S machine. Eur J Pharm Sci 10 267-274, 2000. 

The above table shows that with the exception of capsule size 0 and 5, the amount of powder in grains that can be filled in the capsules can be obtained by subtracting capsule size from the number six. As an example, five grains or 65 x 5 = 325 mg of powdered drug can be filled in capsule size 1. In capsule size 4, 2 gr or approximately 130 mg of the powder can be filled. Capsule size 5 is an exception because it can be filled with one-half to a grain instead of just 1 gr. Similarly, capsule size 0 can be filled with 6-7 gr instead of just the 6 gr. 

In order to fill capsules as a dosage form, the following steps may provide a helpful guide. 

Capsules are dosage forms in which unit doses of powder, semisolid, or liquid drugs are enclosed within a hard or a soft envelope, or shell. Examples of currently compounded capsules are given in Table 1 with the contents as powders, in oil, or in a semisolid-filled capsule, and modified strength capsules. 

Tablets, powder- and liquid-filled capsules Microbial limit test, TAMC, TCYMC only Test development, scale-up and validation batches only 0, 6, 12, 24, 36 months...

The inclusion of the a routine microbial limit test in a marketed product stability protocol depends on the pharmaceutical dosage form. Typically, the test would be used only for nonsterile products, especially oral liquids, nasal sprays, and topical liquids, lotions, and creams that have sufficient water activity to support the growth of microorganisms. In contrast, tablets, powder- and liquid-filled capsules, topical ointments, vaginal and rectal suppositories, nonaqueous liquids and inhalation aerosols with a water activity too low to allow for the product to support the growth of microorganisms would not be routinely tested. 

Usual Digoxin Solution-Filled Capsule Daily Maintenance Dose Requirements (meg)... 

Single oral dose of two 100 mg pellet-filled capsules. 

In a survey of industry practices, Heda (12) found that, as a matter of policy, 46% of the firms sampled favor direct filling of powders as a first choice over granulation prior to filling capsules. Thirty-six percent of firms allow formu-lators to make that decision at their own discretion, whereas 18% of firms favor granulation of all formulations prior to encapsulation. Yet, for half of the firms responding, only 0 10% of their hard shell capsule products are direct-fill powder formulations, and only 27% of firms reported that more than 50% of their capsules were developed as direct-fill formulations. Although some of these non-direct-fill formulations may be controlled release formulations, e.g., barrier-coated bead products, difficult powder formulation problems may, at least in part, account for this observation. 

Table 4 Inhibition of Human Cytochrome P450-Mediated Metabolism by Aliquots of Extracts from Soft Liquid-Filled Capsule Products Containing Echinacea (n > 6 SD 1.25mg/mL Stock Solution Unless Otherwise Stated)...

Each liquid-filled capsule contains 30 mg nimodipine in a vehicle of glycerin, peppermint oil, purified water, and polyethylene glycol 400. The soft gelatin capsule shell... 

Riffino, C. B. Guideline for scale-up of dried filled capsules and tablets. AstraZeneca (Stuart) Pharmaceuticals Internal Document, Feb. 17, 1978. 

Temazepam is a benzodiazepine that was until recently the most popular hypnotic in the form of a soft gel liquid-filled capsule but, being readily injected, it was widely also abused and the formulation was withdrawn. Temazepam is now classed as a controlled drug it is available as a tablet, with a much longer absorption time and duration of action making daytime hangover effect more likely. Consequently it is much less often prescribed. 

J. G. Devane, M. Kavanagh, and J. G, Kelly, Dose proportionality and steady-state bioequivalence of rerapamil sustained-release pellet-filled capsules, Cur. Ther. Res., 50 720-730 (1991). 

All the major machine manufacturers have made machines that can fill capsules with liquids. There are two types of liquid fills formulations of non-aqueous solutions and suspensions and formulations that are liquefied only for the filling process by either heat or shear stress. If the formulation is mobile at ambient temperatures, then the capsules will need to be sealed after filling. 

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