Hydroxypropyl-β-Cyclodextrin and β-Cyclodextrin as Tablet Fillers for Direct Compression

Abstract

Cyclodextrins are cyclic carbohydrates widely used as complexing and non-complexing excipients in drug delivery systems. The purpose of this work was to study the ability of hydroxypropyl-β-cyclodextrin and β-cyclodextrin to act as tablet fillers for direct compression. In this way, several parameters of the cyclodextrins were evaluated, namely: (i) the flow properties such as angle of repose, flow time, Carr index, and Hausner ratio; (ii) the compaction behavior, specifically the energies and forces exerted during tableting, the plasticity index, the lubrication efficiency, and compression profiles (force/time and work/displacement of the upper punch); and (iii) the influence on carbamazepine release characteristics from uncoated tablets, i.e., dissolution rate and disintegration time. In addition, these properties of the cyclodextrins were compared with those from other commonly used direct compression fillers (lactose monohydrate, mannitol, calcium hydrogen phosphate dihydrate, and microcrystalline cellulose) and co-processed excipients (microcrystalline cellulose/mannitol and lactose monohydrate/cellulose). Three main conclusions can be drawn: (i) the studied cyclodextrins can be used as tablet fillers for direct compression; (ii) hydroxypropyl-β-cyclodextrin showed better properties than β-cyclodextrin mainly at the level of the physics of compression (higher values of plasticity index and lubrication efficiency) and of the drug release characteristics (faster and greater dissolution rate and a shorter disintegration time); and (iii) lactose monohydrate and hydroxypropyl-β-cyclodextrin displayed the best results. As there are people intolerant to lactose, hydroxypropyl-β-cyclodextrin, although its cost is higher, can be considered a good substitute for lactose.

Development of Oral Tablets of Nebivolol with Improved Dissolution Properties, Based on Its Combinations with Cyclodextrins

“…However, in this case, the initial drug dissolution rate was also not as fast as expected, with the % dissolved after 10 min being only slightly higher than that from the reference tablet. This last finding could be a consequence of the observed increased hardness and disintegration times of both the tablets containing SBEβCD (see Table 3), which was attributed to the possible binding and compacting properties of this CD, as previously observed for other CDs, including βCD, HPβCD and polymeric CDs [40,41]. Then, in order to verify our hypothesis, a capsule formulation having the same composition of the NEB-SBEβCD COE tablets was prepared, so as to avoid the compression process.…”

“…However, interestingly, tablets containing the drug as received showed a clearly shorter disintegration time with respect to those containing its PM or COE systems with SBEβCD, thus suggesting some binder properties of SBEβCD that slowed down the disintegration process. The binder ability of βCD and of CD polymers has been proved [40], and βCD and HPβCD have been proposed as filler-binder excipients for direct compression [41]. However, it was found that βCD increased the tablets hardness without increasing the disintegration time, since it also acted as a disintegrant agent [42,43].…”

Mechanochemical activation with cyclodextrins followed by compaction as an effective approach to improving dissolution of rutin

“…molecules of the classes II and IV of Biopharmaceutics Classification System (Salústio et al, 2011), this group of excipients also have found a role in tabletting. Several research groups have tested CDs as release-modifying additives, to augment physical and chemical stability of drug molecules, for taste-masking purposes, to reduce or eliminate adverse drug reactions and as single-or multi-functional tablet excipients acting as fillers, disintegrant, binders or showing a combination of these functions (Conceição et al, 2018a(Conceição et al, , 2018bPande and Shangraw, 1995).…”

Physicochemical Profiling of Baicalin Along with the Development and Characterization of Cyclodextrin Inclusion Complexes

“…Self-nanoemulsifying systems, nanocrystals and cyclodextrin complexes were developed to counterbalance the low solubility and concomitant low oral bioavailability of baicalin [15–17]. Cyclodextrins (CDs) are cyclic oligosaccharides composed of α-1,4-linked D-glucopyranose units possessing a hydrophilic exterior and hydrophobic cavity, where lipophilic molecules can form a non-covalently bonded inclusion complex [18]. The cyclodextrin complexation of baicalin is proved to be a promising method to increase its solubility; however, only a limited number of studies were reported, in which hydroxypropyl- β -, and β -CD were used [16, 19].…”