Sustained-release pellet formulations

Fig. 2—Absorption of verapamil after a single dose of a sustained release pellet formulation in six healthy volunteers. The position of the majority of pellets at each blood sampling was detected by X-rays. S, stomach I, intestine C, colon o, fasting , non-fasting.

Farag Y, Leopold CS. Development of shellac-coated sustained release pellet formulations. 

Farag, Y, Leopold, C.S. Development of sheUac-coated sustained release pellet formulations. Eur. J. Pharm. Sci. 42(4), 400-405 (2011)... 

Immediate-release formulations typically consist of the drug substance, fillers such as mannitol and lactose and binders such as gelatin, gelatin hydrolysates, and polyvinylpyrolidone. Cross-linked biopolymers based on collagen derivatives are used for sustained-release pellets. See Refs. ° for a detailed discussion on the formulation and processing variables. 

There are many advantages for choosing to develop and scale-up a capsule formulation over a tablet. As there is no need to form a compact that must withstand rigorous handling, development timelines can be reduced. Encapsulated products allow for easier blinding of clinical supplies and the ability to manufacture unique fills such as tablets in capsules, sustained release pellets, liquids, or semisolids. However, the costs of the capsule shells add an additional expense above the costs of tablet manufacture. 

Considering the above advantages, it is not surprising that HME has quickly foimd numerous applications in pharmaceutical formulation. Since it involves the incorporation or dispersion of an API into a polymer matrix, among its first uses was the formulation of sustained release pellets of freely soluble APIs [5]. Other applications indicative of the method s high popularity and general applicability to various formulation problems are listed below, together with relevant citations ... 

The pharmaceutical and biological availability of eight commercial furose-mide preparations was compared including two products with modified release properties [67], an enteric-coated tablet and a sustained-release preparation, in the form of a capsule containing diffusion pellets [28], A correlation between the rate of dissolution of different techniques and the area under the plasma concentration time curve was documented. The sustained-release preparation and the enteric-coated formulation clearly showed different pharmacokinetic behavior compared with conventional tablets. Although the literature mentions the maximal absorption at pH 5.5, the modified release formulations only showed a relative bioavailability of 80%. 

Glyceryl monostearate is a lubricant for tablet manufacturing and may be used to form sustained-release matrices for solid dosage forms.Sustained-release applications include the formulation of pellets for tablets or suppositories and the preparation of a veterinary bolus. Glyceryl monostearate has also been used as a matrix ingredient for a biodegradable, implantable, controlled-release dosage form. ... 

Many solid-dosage forms of potassium chloride exist including tablets prepared by direct compression and granulation effervescent tablets coated, sustained-release tablets " sustained-release wax matrix tablets micro-capsules pellets and osmotic pump formulations. ... 

Vier-Lopez ME, Nieto-Reyes L. Anguiano-Igea S, et al. Formulation of triamcinolone acetonide pellets suitable for coating and colon targeting. Int J Pharm 1999 179 229-35. Yuen KH, Deshmukh A A. Newton JM. Development and in vitro evaluation of a multiparticulate sustained release theof ylline formulation. Drug Dev Ind f arm 1993 19 855-74. 

In another aspect of the SODAS design, the secondary pellet fraction is produced as described above however, the delayed release beads are produced by coating the IR beads with an enteric polymer (methacrylic acid copolymer) rather than a sustained release polymer (81). This bi-modal release system was used in the formulation of Ritalin LA and was demonstrated to produce two distinct pla.sma concentration peaks separated by approximately 4 hours (81). This bi-modal pulsed release system was demonstrated to be bioequivalent to two immediate release tablet doses administered four hours apart. 

Formulation is a common method of developing sustained release preparations such as erosion tablets, drugs in a waxy matrix (matrix erodes or drug leaches from matrix), coated pellets (different pellets have different release properties), and coated ion-exchange preparations. There are special considerations for sustained release systems, since complicated formulations may be more erratically absorbed the sustained release product may contain a larger dose (and failure of the controlled release mechanism may result in release of a large toxic dose) and is a more expensive technology. 

G.N. Fetih, Formulation and characterization of gelucire pellets for sustained release of Ibuprofen, Bull. Pharm. Sci. 33 (2010) 217-224. 

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