The Use of ß-Cyclodextrin in the Manufacturing of Disintegrating Pellets with Improved Dissolution Performances

Abstract

Abstract. It has recently been highlighted that the release behavior of pellets containing microcystalline cellulose (MCC) as the spheronizing agent may be impaired by the lack of disintegration. Although alternative spheronizing excipients have been proposed, their overall advantages have not thoroughly been assessed. In the present work, the possible use of β-cyclodextrin (βCD) was therefore explored for the manufacturing of pellets with a potential for effective disintegration and immediate release of poorly soluble active ingredients. MCC/βCD powder formulations containing no drug or model drugs with different water solubility, able to form inclusion compounds with the employed cyclodextrin, were pelletized by agglomeration in rotary fluid bed equipment. By applying successive statistical experimental designs, the most critical formulation and operating parameters were identified and optimal manufacturing processes were ultimately set up. High yields of pellets provided with satisfactory physical-technological characteristics were obtained using powder formulations with up to 80% βCD. Based on dissolution testing results, the suitability of βCD for the preparation of disintegrating MCCcontaining pellets with improved dissolution performance was finally demonstrated.

Injection-Molded Capsular Device for Oral Pulsatile Release: Development of a Novel Mold

“…Indeed, while from the fine powder and the granules, containing disintegrant and wetting agents, the drug tracer was promptly available for dissolution, its contact with the aqueous fluid was somewhat delayed because of the reduced surface area exposed by highly dense matrix pellets made of microcrystalline cellulose and coarse fragments of the solid dispersion. 33 An analogous trend was observed with gelatin-based dosage forms with the same contents. With respect to the capsular devices prepared by the former mold, the duration of release (pulse time) was reduced probably due to the relatively lower amount of polymer that has to erode/dissolve to enable the breakup of the capsule.…”

“…On the contrary, some minor differences were found in the release parameters, such as in particular extended lag and pulse times of capsules filled with pellets or with the solid dispersion, which could be attributed to the dissolution behavior of these particular formulations. Indeed, while from the fine powder and the granules, containing disintegrant and wetting agents, the drug tracer was promptly available for dissolution, its contact with the aqueous fluid was somewhat delayed because of the reduced surface area exposed by highly dense matrix pellets made of microcrystalline cellulose and coarse fragments of the solid dispersion 33. An analogous trend was observed with gelatin‐based dosage forms with the same contents.…”

Mono-Dendronized β-Cyclodextrin Derivatives as Multitasking Containers for Curcumin. Impacting Its Solubility, Loading, and Tautomeric Form

“…Among the CDs, βCD (seven glucose units) is the most accessible, inexpensive, and versatile in terms of cavity dimensions; however, its relatively low solubility may hamper its physicochemical and biological performance . Several research groups have focused on overcoming this limitation. − We previously reported a click synthesis of two families of polyester-dendronized βCD compounds [mono- and hepta-substituted derivatives with the first (1G), second (2G), and third (3G) generation dendrons] to improve the solubility and encapsulation performance of native βCD .…”