Different types, applications and limits of enabling excipients of pharmaceutical dosage forms

Palcsó, Barnabás; Zelkó, Romána

doi:10.1016/j.ddtec.2018.04.002

Cited by 9 publications

(5 citation statements)

References 112 publications

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“…A whole number of approaches aimed at improving the poor solubility/dissolution rate exist to date. For example, salts, polymorphs, solvates, hydrates, and co-crystals production [ 10 , 11 , 12 , 13 ]. In addition to this, drug delivery systems involving different pharmaceutically friendly excipients serving as solubilizing and stabilizing agents have not lost actuality from the 19th century to nowadays.…”

Section: Introductionmentioning

confidence: 99%

Another Move towards Bicalutamide Dissolution and Permeability Improvement with Acetylated β-Cyclodextrin Solid Dispersion

2022

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The complex formation of antiandrogen bicalutamide (BCL) with methylated (Me-β-CD) and acetylated (Ac-β-CD) β-cyclodextrins was investigated in buffer solution pH 6.8. A two-fold strongly binding of BCL to Ac-β-CD as compared to Me-β-CD was revealed. The solid dispersion of BCL with Ac-β-CD was prepared by the mechanical grinding procedure to obtain the complex in the solid state. The BCL/Ac-β-CD complex was characterized by DSC, XPRD, FTIR, and SEM techniques. The effect of Ac-β-CD in the BCL solid dispersions on the non-sink dissolution/permeation simultaneous processes was disclosed using the side-by-side diffusion cell with the help of the cellulose membrane. The elevated dissolution of the ground complex, as compared to the raw drug as well as the simple physical mixture, accompanied by the supersaturation was revealed. Two biopolymers—polyvinylpyrrolidone (PVP, Mn = 58,000) and hydroxypropylmethylcellulose (HPMC, Mn ~ 10,000)—were examined as the precipitation inhibitors and were shown to be useful in prolonging the supersaturation state. The BCL/Ac-β-CD complex has the fastest dissolution rate in the presence of HPMC. The maximal concentration of the complex was achieved at a time of 20, 30, and 90 min in the pure buffer, with PVP and with HPMC, respectively. The effectiveness of the BCL dissolution (release) processes (illustrated by the AUCC(T) parameter) was estimated to be 7.8-, 5.8-, 3.0-, and 1.8-fold higher for BCL/Ac-β-CD (HPMC), BCL/Ac-β-CD (PVP), BCL/Ac-β-CD (buffer), and the BCL/Ac-β-CD physical mixture, respectively, as compared to the BCL_raw sample. The excipient gain factor (EGF), calculated for the dissolution of the BCL complex, was shown to be 2.6 in the presence of HPMC, which is 1.3-fold greater as compared to PVP. From the experimental dissolution results, it can be concluded that the formation of BCL ground complex with Ac-β-CD enhances the dissolution rate of the compound. The permeation was also shown to be advantageous in the presence of the polymers, which was demonstrated by the elevated fluxes of BCL through the membrane. The comparison of the dissolution/permeation processes was illustrated and discussed. The conclusion was made that the presence of HPMC as a stabilizer of the supersaturation state is promising and seems to be a useful tool for the optimization of BCL pharmaceutical formulations manufacturing.

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Section: Introductionmentioning

confidence: 99%

Another Move towards Bicalutamide Dissolution and Permeability Improvement with Acetylated β-Cyclodextrin Solid Dispersion

2022

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“…Along with the development of novel drug delivery conventional and novel synthetic or natural excipients provide opportunities to design dosage forms with the required features including their bioavailability [23]. In the composition design of polymeric micelles amphiphilic micelle forming graft copolymer Soluplus ® was chosen, due to its advantageous properties: low CMC value in water, mucoadhesion, biodegradability.…”

Section: Introductionmentioning

confidence: 99%

Quality by Design Based Formulation Study of Meloxicam-Loaded Polymeric Micelles for Intranasal Administration

et al. 2020

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Our study aimed to develop an “ex tempore” reconstitutable, viscosity enhancer- and preservative-free meloxicam (MEL)-loaded polymeric micelle formulation, via Quality by Design (QbD) approach, exploiting the nose-to-brain pathway, as a suitable tool in the treatment of neuroinflammation. The anti-neuroinflammatory effect of nose-to-brain NSAID polymeric micelles was not studied previously, therefore its investigation is promising. Critical product parameters, encapsulation efficiency (89.4%), Z-average (101.22 ± 2.8 nm) and polydispersity index (0.149 ± 0.7) and zeta potential (−25.2 ± 0.4 mV) met the requirements of the intranasal drug delivery system (nanoDDS) and the targeted profile liquid formulation was transformed into a solid preservative-free product by freeze-drying. The viscosity (32.5 ± 0.28 mPas) and hypotonic osmolality (240 mOsmol/L) of the reconstituted formulation provides proper and enhanced absorption and probably guarantees the administration of the liquid dosage form (nasal drop and spray). The developed formulation resulted in more than 20 times faster MEL dissolution rate and five-fold higher nasal permeability compared to starting MEL. The prediction of IVIVC confirmed the great potential for in vivo brain distribution of MEL. The nose-to-brain delivery of NSAIDs such as MEL by means of nanoDDS as polymeric micelles offers an innovative opportunity to treat neuroinflammation more effectively.

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“…Other papers have paid little attention to the distribution of the active ingredient in the tablet (Cook et al, 2004;Elliott et al, 2014). It is relevant to recall that in addition to the drug, excipients are also added to the formulation ( Haywood & Glass, 2011;Palcsó & Zelkó, 2018), and as they are mixed together it makes it difficult to know the active ingredient distribution in the tablet . This raises the question of whether the patients are taking mostly the drug or the excipients.…”

Section: Discussionmentioning

confidence: 99%

The practice of dividing tablets: An uncertain act

Pareja¹,

Manrique²,

Gualdron³

et al. 2022

ijp

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Background and Aims: Tablets can be split by patients for a number of reasons, using various instruments. Tablets can be scored or unscored; if scored, they may be split into pieces, and in spite of guidelines to do so patients are still at risk of resultant drug dose fluctuations, or being exposed to toxic or subtherapeutic doses. The aim of this study was to investigate differences in weight between halves of tablets, split by different populations and with different devices. Methods: 3-factor full factorial design (3 runs) was used with participants: patients, caregivers, nurses, medical doctors, and pharmacists; instruments: scissors, tablet cutters, knives, hand; drugs: losartan, clonidine, metoprolol, and warfarin. The risk of unequal tablet splitting was estimated and analyzed for each factor and their interaction with linearized generalized models. Results: Differences in weight were found to be above 15% and 25% of the theoretical weight as in general, the highest weight variations after splitting were found in clonidine with patients using scissors. The overall risk of non-equal tablet splitting was 22.5% for deviations > 15% and for > 25%. Conclusion:In this study, no tablet was split into halves of equal weight; based on these findings, splitting tablets is a questionable practice.

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Different types, applications and limits of enabling excipients of pharmaceutical dosage forms

Cited by 9 publications

References 112 publications

Another Move towards Bicalutamide Dissolution and Permeability Improvement with Acetylated β-Cyclodextrin Solid Dispersion

Another Move towards Bicalutamide Dissolution and Permeability Improvement with Acetylated β-Cyclodextrin Solid Dispersion

Quality by Design Based Formulation Study of Meloxicam-Loaded Polymeric Micelles for Intranasal Administration

The practice of dividing tablets: An uncertain act

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