Capsules formulation

Capsule Formulations. Expert systems for capsule formulation have been developed by personnel at the University of London in collaboration with Capsugel and Sanofl Research Division in Philadelphia. 

The system developed by personnel at Sanofl uses the Formulogic shell with specific preformulation data on the drug. The system recommends one first-pass clinical capsule formulation with as many subsequent formulations as desired to accommodate an experimental design [24]. An example of a formulation proposed for naproxen at a dose of 500 mg is shown in Table 28.2. In addition to the formulation the system provides advice on the milling of the drug, the process to be used for blending, and details of the capsule shell. 

Lai S, Podczeck F, Newton JM, Daumesnil R. An expert system to aid the development of capsule formulations. Pharm Tech Eur 1996 12(9) 60-8. 

Bateman SD, Verlin J, Russo M, Guillot M, Laughlin SM. The development and validation of a capsule formulation knowledge based system. Pharm Tech 1996 20(3) 174-84. 

J. C. Samyn and W. Y. Jung, In vitro dissolution from 39. several experimental capsule formulations, J. Pharm. 

G. Design of Hard Gelatin Capsule Formulations for Powder Fill... 

Capsule formulations usually require lubricants just as do tablet formulations. Lubricants ease the ejection of plugs, reduce filming on pistons and adhesion of powder to metal surfaces, and reduce friction between sliding surfaces in contact with powder. The same lubricants are used in both tablet and capsule formulations. 

Surfactants may be included in capsule formulations to increase the wetting of the powder mass and enhance... 

AG Stewart, DJW Grant, JM Newton. The release of a model low-dose drug (riboflavine) from hard gelatin capsule formulations. J Pharm Pharmacol 31 1-6,1979. 

KS Murthy, JC Samyn. Effect of shear mixing on in vitro drug release of capsule formulations containing lubricants. J Pharm Sci 66 1215-1219, 1977. 

Chewable tablets and sprinkle capsule formulations have been very well received by both patients and their parents for use in children with full dentition (older than 3 years, [75-77]. This is potentially a very fruitful area for future research and development. Pharmaceutical preparations developed for administration to young children need to have consistent bioavailability when administered with food [78]. 

John et al. [37] described a colorimetric method for the estimation of primaquine phosphate. Sample solutions of different dilutions (0.15-0.6 mL) of the drug (6-24 pg/mL) were treated with 5 mL of 1% cerric ammonium sulfate in dilute nitric acid and made up to 25 mL with water. The absorbance of the resulting light purple solution was measured at 480 nm after similar 30 min. Beer s law was obeyed from 5 30 pg/mL of primaquine phosphate. The method is applicable to bulk formulations in addition to tablets and capsule formulation. 

It is enough to visit the clean, small production plant of Sol-Gel Technologies in Israel (Figure 8.3) to recognize that most of the value added to benzoyl peroxide entrapped in microcapsules comes from knowledge—and thus from human ingenuity—which originates the production of the microcapsules. The price at which the white water-based capsule formulation is sold to customers exceeds more than 1000 times the price of the raw materials used to prepare it. Put another way ... 

Ritonavir is a product of Abbott Laboratories Ltd. for the treatment of HIV and is marketed as Norvir , in liquid and semisolid capsule formulations. It received FDA approval for market launch in march 1996, at which time only one polymorphic form of Ritonavir (Form I) was known. Two years later in early 1998 a laboratory responsible for testing the formulated product in the US reported dissolution test failures of the semisolid capsules, and noted that drug product had precipitated out of solution. A new polymorphic form had been discovered that was thermodynamically more stable than the existing form and approximately 5 times less soluble in the formulation. Figure 7. 

Perkins AC, Wilson CG, Frier M, Vincent RM, Blackshaw PE, Danserau RJ, Juhlin KD, Bekker PJ, Spiller RC. Esophageal transit of risedronate cellulose-coated tablet and gelatin capsule formulations. Int J Pharm 1999 186 169-175. 

Currently, the Japanese Pharmacopoeia (JP) is the only pharmacopeia that requires a specific sinker device for all capsule formulations. The USP recommends a few turns of a nonreac-tive material wire when the dosage form tends to float (12) (see Chapter 2 for illustrations of the Japanese and USP sinkers). Because sinkers can significantly influence the dissolution... 

Ramsay-Olocco K, Alexandrova L, Nellore R, Killion R, Li L, Coen P, Ho Q, Jung D, Rocha C (2004) Pre-clinical and clinical evaluation of solution and soft gelatin capsule formulations for a BCS class 3 compound with atypical physicochemical properties. J Pharm Sci 93 2214—2221... 

Cupissol, D., Bressolle, F., Adenis, L., Carmichael, J., and Romain, D., Evaluation of the bioequivalence of tablet and capsule formulations of granisetron in patients undergoing cytotoxic chemotherapy for malignant disease, /. Pharm. Sci., 82, 1281,1993. 

Wilson, W.I., Peng, Y., and Augsburger, L.L. Generalization of a prototype intelligent hybrid system for hard gelatin capsule formulation development, Pharm. Sci. Tech., 6(3) E449-E457, 2005. 

Chatterjee A, Digumarti R, Katneni K, Upreti VV, Mamidi RN, Mullangi R, Surath A, Sriniva ML, Uppalapati S, Jiwatani S, Srinivas NR. (2005) Safety, tolerability, and pharmacokinetics of a capsule formulation of DRF-1042, a novel camptothecin analog, in refractory cancer patients in a bridging phase 1 study. J Clin Pharmacol 45 453 60. 

Angina patients maintained on the nifedipine capsule formulation may be switched to the sustained release tablet at the nearest equivalent total daily dose. Experience with doses more than 90 mg in angina is limited. 

Pharmacokinetics Peak concentrations of ritonavir were achieved approximately 2 and 4 hours after dosing under fasting and nonfasting conditions, respectively. The extent of absorption of ritonavir from the capsule formulation was 15% higher when administered with a meal. 

Pregnancy Category C. Amprenavir oral solution is contraindicated during pregnancy because of the potential risk of toxicity to the fetus from the high propylene glycol content. Therefore, if amprenavir is used in pregnant women, use the capsule formulation. 

If patients require treatment with amprenavir oral solution, monitor them closely for propylene glycol-associated adverse reactions, including seizures, stupor, tachycardia, hyperosmolality, lactic acidosis, renal toxicity, and hemolysis. Switch patients from amprenavir oral solution to capsules as soon as they are able to take the capsule formulation. 

In 1995 the FDA approved saquinavir, the first protease inhibitor, for use in combination with other nucleoside analogue medications. In 1999 a soft gel capsule formulation of saquinavir with considerably improved absorption characteristics was developed. Ritonavir and indinavir have been approved for use alone or in combination with nucleoside analogue medications in people with advanced HIV disease. Nelfinavir is the first protease inhibitor labeled for use in children. Amprenavir is the newest of the protease inhibitors. Amprenavir can be taken with or without food, but it should not be taken with a high-fat meal because the fat content may decrease the absorption of the drug. The most disturbing adverse reactions to protease inhibitors consist of the lipodystrophy syndrome with severe hyperlipidemia and unpredictable fat redistributions over the body... 

For children who can swallow capsules and for whom the current capsule formulations allow appropriate weight or body surface area calculated dosing, additional options to replace LPV/r include SQV/r and IDV/r. 

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