Liquid filling 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. 

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... 

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form of a soft gel liquid-filled capsule but, being readily injected, it was widely also abused and the formulation was withdrawn.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. 

Ethchlorvynol is marketed as a liquid-filled capsule with a polyethylene glycol diluent. Toxicity has resulted from oral overdose and from intravenous injection of the liquid contents of a capsule. 

Table 1. Reasons for developing an oral solution or a liquid-filled capsule.

Capsules typically vary in volume from 0.5-1.5 mL, but the ideal volume filled into a capsule is approximately 0.7 mL to allow for an easily swallowed capsule. Thus ideally the entire dose of active ingredient should be solubilized in a total volume of less than or equal to 0.7 mL to allow for a dose regimen of 1 capsule per dose (Liu, 2000), otherwise a larger capsule is required, or a dose regimen of multiple capsules per dose must be considered. The dose range of active ingredients in capsule formulations is from 0.25 pg to 500 mg, and the upper mass of an entire liquid-filled capsule is about 1650 mg. Both soft and hard gelatin capsules are used for solubilized oral formulations. Liquid formulations can be filled into either soft or hard capsules, whereas semisolids or solid formulations are filled into hard capsules. 

A mixture of medium-chain triglycerides, polyethyleneglycol, and propylene glycol solubilizes the combination of 250 mg of acetaminophen, 10 mg of dextromethorphan HBr, 100 mg of guaifenesin, and 30 mg of pseudoephedrine HCl in over-the-counter Robitussin Cold, Cough Flu liquid-filled capsules. 

A clinical formulation of cyclosporin that was shown to be bioequivalent to Neoral used a liquid-filled capsule formulation that spontaneously forms a nanosuspension when mixed in an aqueous media (Bekerman et al., 2004). The liquid vehicle is composed of 200 mg of cyclosporin dissolved in a mixture of 800 pL of organic solvent [NMP (N-methylpyrrolidone), PG and/or PEG], 140 mg of egg phosphatidylcholine, 540 pL of Tween 80,... 

YePesid concentrate for injection 20 mg/mL, liquid-filled capsules for oral use 50 mg, Toposar concentrate for injection 20 mg/mL, liquid-filled capsules for oral use 50 mg, Etopophos powder for injection 100 mg vial)... 

A liquid-filled capsule shell should also remain flexible. Furthermore, after removing the contents of the capsule (by expressing the liquid), the analyst should open up the capsule to look for evidence of particulate matter (crystallization of active ingredient) and for unusual discoloration of the interior of the capsule shell. 

Information is very limited, but the interaction seems to be established. It is not likely to occur with solid form, fast-dissolving digoxin preparations (e.g. liquid-filled capsules) or digoxin in liquid form, but only with those preparations which are slowly dissolving (i.e. some tablet formulations). A reduction in digoxin levels of one-third could result in under-digitalisation. There seems to be no information about digitoxin. 

This class of polymerization type is similar to an emulsion and suspension polymerization, however, it is mostly commonly employed for polycondensation reactions. An interfacial polymerization reaction occurs at or near the interfacial boundary of two immiscible solutions. The two reagents meet at the interface and react rapidly. The basis for this method is from the Schotten-Baumann reaction between an acid chloride and a compound containing an active hydrogen atom. Under the right conditions thin flexible walls of alternating copolymer form rapidly at the interface to form liquid-filled capsules (Scott et al, 2005. These capsules (about 210 nm) have been explored as direct and efficient encapsulation devices, given that their nanometer thick shells (about lOnm) and confined liquid-core domain, offer unique sequestration potential compared to conventional polymer nanoparticles. It has been proposed that... 

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