Abstract：
:Minitablets are an appealing option for an age-appropriate pediatric dosage form. In particular, for combination therapies where multiple active ingredients are dosed simultaneously, the use of minitablets will enable independent adjustments of each dose. The work presented describes the development of Compound A and Compound B minitablets for a combination therapy. Since both actives are formulated as spray dried amorphous solid dispersions (ASDs) due to low solubility of their crystalline forms, the choice of minitablets for the pediatric dosage form allows the application of the same formulation strategy across different age groups. To address the potential need for taste-masking, an ethylcellulose-hydroxypropyl cellulose coating system was developed. In-vitro performance testing was conducted to guide coating development and to ensure proper taste-masking without slowing down API dissolution in the GI tract that can negatively impact exposures. As a result, the exposure of orally dosed coated tablets was comparable to those of uncoated minitablets in the canine model. The work presented can serve as a case study on how minitablets can be designed and developed as an appropriate pediatric dosage form for a combination therapy comprised of ASD of active ingredients.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Zhang D,Rumondor ACF,Zhu W,Colace T,Marota M,Mora J,Liu Z,Li Ydoi
10.1016/j.xphs.2020.08.021subject
Has Abstractpub_date
2020-12-01 00:00:00pages
3590-3597issue
12eissn
0022-3549issn
1520-6017pii
S0022-3549(20)30491-3journal_volume
109pub_type
杂志文章abstract：:The solubility of a drug is ultimately governed by its chemical potential as it is present in the undissolved solute. For a pharmaceutical amorphous solid dispersion (ASD), its solubility depends on the state and composition of the undissolved solute when the ASD is equilibrated with water. Concerning the undissolved ...
journal_title：Journal of pharmaceutical sciences
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doi：10.1016/j.xphs.2016.08.017
更新日期：2016-12-01 00:00:00
abstract：:The chemical stability of the novel anticancer agent carzelesin in aqueous buffer/acetonitrile (1:1, v/v) mixtures has been investigated utilizing a stability-indicating reversed-phase high-performance liquid chromatographic assay. The degradation kinetics of carzelesin has been studied as a function of pH, buffer com...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1021/js960005n
更新日期：1996-11-01 00:00:00
abstract：:The extent of formation of solasodiene from solasodine upon treatment with hydrochloric acid under various conditions was determined. The diene formed was assayed by using the characteristic extinction at 236 nm. Diene formation was effected by the acid concentration and the boiling point of the solvent used. Optimal ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600670839
更新日期：1978-08-01 00:00:00
abstract：:A modification of wet agglomeration technique is developed and demonstrated by agglomerative crystallization process for a nonapeptide (ABT-510) to improve processing of needle like crystals. Our procedure involves exploiting partial miscibility of the crystallization solvent system for in situ generation of a wetting...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.21063
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abstract：:Benzyl alcohol (BA) is the most widely used antimicrobial preservative in multidose protein formulations, and has been shown to cause protein aggregation. Our previous work on a model protein cytochrome c demonstrated that this phenomenon occurs via partial unfolding. Here, we examine the validity of these results by ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.24105
更新日期：2015-02-01 00:00:00
abstract：:We report a programed drug delivery system that can tailor the release of anesthetic bupivacaine in a spatiotemporally controlled manner. The drug delivery system was developed through the combination of a collagen-based injectable hydrogel and 2 types of poly(lactic-co-glycolic acid) (PLGA) particles. As a rapid-rele...
journal_title：Journal of pharmaceutical sciences
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doi：10.1016/j.xphs.2016.09.020
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abstract：:The pKa values of benzoic acid, p-methylbenzoic, and p-aminobenzoic acid (PABA) were determined by potentiometric titration in mixtures of 0-0.5 volume fractions of various cosolvents and water. The differences between the aqueous and semiaqueous pKa values were similar for the three solutes at a particular cosolvent-...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600750217
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abstract：:The ICH Q1B guidance and additional clarifying manuscripts provide the essential information needed to conduct photostability testing for pharmaceutical drug products in the context of manufacturing, packaging, and storage. As the previous 2 papers in this series highlight for drug products administered by injection (...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章,评审
doi：10.1016/j.xphs.2016.02.035
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abstract：:The aims of this study were to evaluate the pharmacokinetics of doripenem (Finibax®, Doribax®, S-4661), a parenteral carbapenem antibiotic, in pediatric patients based on concentrations of doripenem in plasma after administration of 20 mg/kg 2 or 3 times daily and to evaluate the dosing regimens by using Monte-Carlo p...
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doi：10.1016/j.xphs.2019.04.002
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abstract：:A representative series of hydroxy-5 beta-cholanyl-24-amines were tested both in vitro and in vivo with respect to their activity against the intestinal bacteria responsible for bile acid metabolism. For the in vitro studies, radiolabeled [14C]cholic acid was incubated with human stools both in aerobic and anaerobic c...
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pub_type： 杂志文章
doi：10.1002/jps.2600810310
更新日期：1992-03-01 00:00:00
abstract：:The stability of aqueous solutions of luteinizing hormone-releasing hormone (LHRH) after extended storage at various temperatures was investigated using a newly developed HPLC assay and an in vitro dispersed pituitary cell culture bioassay. Good correlations were obtained between the potency obtained by HPLC and bioas...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600730628
更新日期：1984-06-01 00:00:00
abstract：:The dissolution kinetics of theophylline monohydrate and anhydrous theophylline were investigated with a rotating-disk apparatus in buffer solutions at 298 K under sink conditions. The observed dissolution rate of theophylline monohydrate under various conditions agreed well with predictions based on the Extended Simu...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600750515
更新日期：1986-05-01 00:00:00
abstract：:Capillary gas chromatography using an open tubular fused silica column and NP-FID was applied to the simultaneous analysis of the antihistamine, carbinoxamine, and the antitussive, hydrocodone, in human serum. Carbinoxamine and hydrocodone were extracted into methylene chloride-2-propanol (9:1) under alkaline conditio...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600721126
更新日期：1983-11-01 00:00:00
abstract：:Partial molal volumes (Vi infinity) of physostigmine, ranging from 232.9 to 239.8 cm3.mol-1, and its mole fraction solubilities (Xi), ranging from 0.051 to 0.009, were determined at 25 degrees C in solutions of isopropanol (IPA), isopropyl myristate (IPM), and their mixtures. An inverse relation was found between Vi i...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600800615
更新日期：1991-06-01 00:00:00
abstract：:The pharmacokinetics of atropine in three healthy male volunteers after intravenous administration of 1.35 and 2.15 mg of the drug was determined. Pharmacodynamic effects of atropine were measured simultaneously. All the data were fitted to a novel integrated kinetic-dynamic model. Plasma concentrations of atropine an...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600740702
更新日期：1985-07-01 00:00:00
abstract：:Dissolving microneedle patches offer promise as a simple, minimally invasive method of drug and vaccine delivery to the skin that avoids the need for hypodermic needles. However, it can be difficult to control the amount and localization of drug within microneedles. In this study, we developed novel microneedle design...
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pub_type： 杂志文章
doi：10.1002/jps.22140
更新日期：2010-10-01 00:00:00
abstract：:Release characteristics of two ethylated beta-cyclodextrins [heptakis(2,6-di-O-ethyl)-beta-cyclodextrin (diethyl-beta-cyclodextrin) and heptakis(2,3,6-tri-O-ethyl)-beta-cyclodextrin (triethyl-beta-cyclodextrin)] as sustained-release drug carriers were evaluated using diltiazem hydrochloride, a water-soluble calcium an...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600790211
更新日期：1990-02-01 00:00:00
abstract：:A general method for predicting the intestinal absorption of a wide range of drugs using multiple regression analysis of their physicochemical properties and the drug-membrane electrostatic interaction was developed. The absorption rates of tested drugs from rat jejunum were measured by the in situ single-pass perfusi...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1021/js970451q
更新日期：1998-08-01 00:00:00
abstract：:Dose individualization is essential in epilepsy treatment, especially in antiepileptic drugs that present high interindividual variability such as lamotrigine. We aimed an observational study to develop a population pharmacokinetic model for quantitative evaluation of the factors that influence lamotrigine pharmacokin...
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更新日期：2020-09-01 00:00:00
abstract：:The effects of physical aging and antiplasticization on the water transport properties of glassy cellulose acetate film-coated tablets were investigated. The gradual approach toward thermodynamic equilibrium during physical aging decrease the free volume of the polymers. This decrease in free volume is accompanied by ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600830337
更新日期：1994-03-01 00:00:00
abstract：:Vitamin E tocopherol polyethylene glycol succinate (TPGS) is a non-ionic surface active agent, known to enhance the bioavailability of lipophilic compounds via wettability, solubility, and in some cases permeability enhancement. MK-0536 is an anti-retroviral drug with poor wettability and solubility and a high dose. B...
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journal_title：Journal of pharmaceutical sciences
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更新日期：1995-09-01 00:00:00
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更新日期：2004-01-01 00:00:00
abstract：:The results of this study show that pentamidine isethionate (PI) can exist in at least four crystalline forms-three anhydrates designated as forms A, B, and C, and a trihydrate. Form C is the high-temperature modification, produced by heating forms A, B, and the trihydrate above 130 degrees C and cannot be produced un...
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更新日期：2011-06-01 00:00:00
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更新日期：2001-07-01 00:00:00
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更新日期：2010-02-01 00:00:00
abstract：:3-Fluoro-, 3-chloro-, and 3-bromocyclophosphamide were prepared from the reaction of trifluoromethylhypofluorite, sodium hypochlorite, and bromine with the anticancer drug cyclophosphamide. Treatment of cis- and trans-4-phenylcyclophosphamide and 5,6-benzocyclophosphamide with sodium hypochlorite afforded cis- and tra...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600720622
更新日期：1983-06-01 00:00:00
abstract：:Ketoconazole and posaconazole are both Biopharmaceutics Classification System class 2 drugs (highly permeable, poorly soluble), are structurally similar, and are administered at the same doses. Nevertheless, the duodenal concentration profile and the magnitude of the positive food effect observed for these 2 drugs are...
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