A new dual function orodissolvable/dispersible meclizine HCL tablet to challenge patient inconvenience: in vitro evaluation and in vivo assessment in human volunteers.

Meclizine hydrochloride (MCZ), a first-generation antihistamine of the piperazine class, is antiemetic and intended for the management of nausea and vomiting with few adverse effects. The introduction of orodispersible tablet (ODT) would solve the problems encountered in the administration of this drug to pediatric, geriatric, and psychiatric patients. It would be even more advantageous if the MCZ tablet could provoke rapid and prolonged efficacy. Achieving concomitant rapid and prolonged drug therapeutic effects in orodissolvable/dispersible dosage forms would be challenging. In this respect, the authors prepared tablets with coats and cores for immediate and prolonged drug absorption. To achieve this goal, nanoparticles of MCZ from chitosan (CS) and shellac (SH) were prepared by ionic crosslinking and then directly compressed with excipients to form the core in a coated tablet. The immediate release coat with MCZ with the same excipients as in the core was amenable by direct compression. MCZ in the coat dissolved in the presence of a superdisintegrant, leading to rapid absorption from the buccal cavity. Meanwhile, enteric-coated nanoparticles were swallowed and dissolved in the GIT. Intuitively, the absorption process was prolonged. The in vitro release characteristics of all the tablets were studied in comparison with a commercial tablet (CT). Additionally, evaluation of the in vivo pharmacokinetic profile of both the prepared and commercial tablets was performed in humans. The dual function tablet disintegrated in 58 s at pH 5.5. In vivo, noncompartmental pharmacokinetic analysis showed concomitant rapid absorption, possibly from the coat, followed by prolonged absorption from the core. Successfully, these good results confirm that combined rapid and prolonged MCZ therapy with the prepared dual function orodissolvable/dispersible tablet could be a promising oral drug delivery system to enhance convenience for patients. Hopefully, dual function tablets will confer a benefit through the accommodation of more than a single medication in the case of multiple therapies.

New Perspective Enteric-Coated Tablet Dosage Form for Oral Administration of Ceftriaxone: In Vitro and In Vivo Assessments.

Ceftriaxone (CTX) is a widely used injectable third-generation cephalosporin that exhibits broad-spectrum antibacterial activity. Unfortunately, the oral route of this drug suffers different encumbrances, such as instability in the upper part of the GIT and enzymatic degradation, as well as poor permeability. There is no reported tablet dosage form for this drug. In this respect, the authors investigated the possibility of developing an enteric-coated oral tablet of CTX that would be helpful for better patient compliance. The tablet consists of directly compressed core of CTX, citric acid (CA), sodium chloride (NaCl), and two biopolymers-chitosan (CH), a permeation enhancer, and silicified microcrystalline cellulose (SMCC), a wicking agent. Both biopolymers are naturally occurring polysaccharides that are biodegradable in the colon and able to incorporate acid labile drugs. CA is a pH modulator to protect CTX from protease enzymes, while NaCl is a translocation enhancer that helps drug penetration. The enteric coat of the core was shellac (SH) with plasticizer glycerol tristearate (GTS) and CA that was applied by direct compression (dry coating). The solventless heat curable coat resulted in an enteric-coated tablet that complies with the USP pharmacopeia. The optimized formula was further subjected to in vitro release and stability studies, as well as ingredient compatibility. In vivo oral bioavailability of the enteric-coated tablets in rabbits gave promising results (absolute bioavailability of about 80%). Synergistically, all ingredients together augmented oral bioavailability of CTX. This developed formula could be a perspective delivery system for those drugs intended to be absorbed from the colon such as peptides and peptide-like drugs.

Improvement of dissolution and hypoglycemic efficacy of glimepiride by different carriers.

Effects of tromethamine (Tris), polyvinylpyrrolidone (PVP-K25), and low molecular weight chitosan (LM-CH) on dissolution and therapeutic efficacy of glimepiride (Gmp) were investigated using physical mixtures (PMs), coground mixtures, coprecipitates (Coppts) or kneaded mixtures (KMs), and compared with drug alone. Fourier transform infrared spectroscopy, differential scanning colorimetry, and X-ray diffractometry were performed to identify any physicochemical interaction with Gmp. Surface morphology was examined via scanning electron microscopy. The results of Gmp in vitro dissolution revealed that it was greatly enhanced by Coppt with Tris or PVP-K25 and KM with LM-CH at a drug to carrier ratio of 1:8. Gmp amorphization by PVP-K25 and LM-CH was a major factor in increasing Gmp dissolution. Being basic, Tris might increase the pH of the microdiffusion layer around Gmp particles improving its dissolution. Formation of water-soluble complexes suggested by solubility study may also explain the enhanced dissolution. Capsules were prepared from Coppts and KM 1:8 drug to carrier binary systems and also with Tris PMs. In vivo, the hypoglycemic efficacy of Gmp capsules in rabbits increased by 1.63-, 1.50-, and 1.46-fold for 1:8 Coppts with Tris or PVP-K25 and KM with LM-CH respectively, compared with Gmp alone. Surprisingly, the response to Tris PM 1:20 capsules was 1.52-fold revealing statistically insignificant difference to that of Tris Coppt 1:8 (1.63 fold). As a conclusion, dissolution enhancement and hypoglycemic potentiation by 1:20 PM of Gmp/Tris, being simple and easy to prepare, may enable development of a reduced-dose and fast-release oral dosage form of Gmp.

Vorinostat with sustained exposure and high solubility in poly(ethylene glycol)-b-poly(DL-lactic acid) micelle nanocarriers: characterization and effects on pharmacokinetics in rat serum and urine.

The histone deacetylase inhibitor suberoylanilide hydroxamic acid, known as vorinostat, is a promising anticancer drug with a unique mode of action; however, it is plagued by low water solubility, low permeability, and suboptimal pharmacokinetics. In this study, poly(ethylene glycol)-b-poly(DL-lactic acid) (PEG-b-PLA) micelles of vorinostat were developed. Vorinostat's pharmacokinetics in rats was investigated after intravenous (i.v.) (10 mg/kg) and oral (p.o.) (50 mg/kg) micellar administrations and compared with a conventional polyethylene glycol 400 solution and methylcellulose suspension. The micelles increased the aqueous solubility of vorinostat from 0.2 to 8.15 ± 0.60 and 10.24 ± 0.92 mg/mL at drug to nanocarrier ratios of 1:10 and 1:15, respectively. Micelles had nanoscopic mean diameters of 75.67 ± 7.57 and 87.33 ± 8.62 nm for 1:10 and 1:15 micelles, respectively, with drug loading capacities of 9.93 ± 0.21% and 6.91 ± 1.19%, and encapsulation efficiencies of 42.74 ± 1.67% and 73.29 ± 4.78%, respectively. The micelles provided sustained exposure and improved pharmacokinetics characterized by a significant increase in serum half-life, area under curve, and mean residence time. The micelles reduced vorinostat clearance particularly after i.v. dosing. Thus, PEG-b-PLA micelles significantly improved the p.o. and i.v. pharmacokinetics and bioavailability of vorinostat, which warrants further investigation.