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ACS Omega ; 3(2): 2406-2416, 2018 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-30023832


The objective of pharmaceutical cocrystallization is to create crystalline analogues that have vastly different properties, such as solubility, melting point, stability, and bioavailability from that observed in the pure active pharmaceutical ingredients (APIs). Amoxapine is a benzoxazepine derivative and exhibits antidepressant properties. Amoxapine has very low solubility in water, so it was cocrystallized with natural acids in a 1:1 ratio in appropriate solvents by the solvent-drop grinding method. Single crystals of cocrystals were grown by the solvent evaporation method in water, ethanol, and methanol. Crystal structures of API salts were determined by single-crystal X-ray diffraction. Salts were characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, and powder X-ray diffraction. Solubility of salts was determined in water by the shake-flask method at 37 °C using UV-vis spectroscopy. Salts of amoxapine with different acids were successfully developed, and their crystal structure was determined. Enhanced solubility was found in the salts of amoxapine for pharmaceutical application in drug formulation.

J Org Chem ; 82(23): 12763-12770, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29020451


A metal-free highly diastereoselctive [3 + 2] cycloaddition reaction has been developed between N-phenacylbenzothiazolium bromides and prochiral cyclopentene-1,3-diones. The active 1,3 dipole benzothiazolium N-phenacylide was generated in situ with the treatment of DIPEA, and the corresponding cycloaddition products were obtained in excellent yields under mild reaction conditions. The scope of the reaction is quite broad, tolerating a variety of aryl and heteroaromatic groups. A catalytic asymmetric approach was also studied preliminarily, and moderate enantioselectivity was achieved.

Mater Sci Eng C Mater Biol Appl ; 75: 1376-1388, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28415429


The purpose of study was to conjugate and evaluate methotrexate with C60-fullerenes and multi-walled carbon nanotubes (MWCNTs) for better drug delivery to cancer cells, and also to compare these two systems. C60-fullerenes and MWCNTs were functionalized by 1,3-dipolar cycloaddition using glycine and paraformaldehyde. Methotrexate (MTX) was esterified and conjugated to the functionalized carbon-based carriers. The conjugates were characterized for micromeritics and drug conjugation. The systems were evaluated for drug release in various pH, MTT cytotoxicity assay, protein binding, cellular uptake, haemolytic profile and pharmacokinetics. Spectroscopic studies confirmed the successful conjugation of drug to the aminated carbon-based carriers. The developed systems released more drug at the pH of cancer cells to that of the pH of plasma. The carriers were compatible with erythrocytes and offered substantial cytotoxicity. Better cellular uptake was confirmed by confocal laser scanning microscopy. C60-fullerenes/MWCNTs modulated the pharmacokinetic profile of drug in desired manner, resulting in better retention and compartment availability. However, the results from C60-fullerenes were observed to be better than that from MWCNTs. The present findings established the potential of carbon-based aminated nanocarriers for delivery of methotrexate in safer and effective manner.

Neoplasias da Mama/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Fulerenos , Metotrexato , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Feminino , Fulerenos/química , Fulerenos/farmacocinética , Fulerenos/farmacologia , Humanos , Metotrexato/química , Metotrexato/farmacocinética , Metotrexato/farmacologia
Int J Pharm ; 495(1): 551-559, 2015 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-26383841


Docetaxel has always attracted the researchers owing to its promises and challenges. Despite marked efficacy, concerns like poor aqueous solubility, lower bioavailability, poor tissue penetration and dose related side-effects offer further scope of research on docetaxel. The present study aims to explore the potential of C60-fullerenes in the delivery of docetaxel to cancerous cells. C60-fullerenes were carboxylated, acylated and conjugated with the drug. The chemical processes were monitored by UV, FT-IR and NMR spectroscopy. The conjugate was further characterized for drug loading, micromeritics, drug release, morphology and evaluated for in-vitro cytotoxicity, haemolysis and in-vivo pharmacokinetic profile. The developed nanoconstruct was able to enhance the bioavailability of docetaxel by 4.2 times and decrease the drug clearance by 50%. The developed system was able to control the drug release and was found to be compatible with erythrocytes. The cytotoxic potential on studied MCF-7 and MDA-MB231 cell lines was also enhanced by many folds, indicating marked promise in efficacy enhancement and dose reduction. The present findings are encouraging and offer a technique to enhance the delivery and efficacy potential of anticancer agents, especially belonging to BCS class IV.

Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Fulerenos/química , Taxoides/administração & dosagem , Taxoides/farmacocinética , Animais , Apoptose , Química Farmacêutica/métodos , Docetaxel , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Humanos , Células MCF-7 , Taxa de Depuração Metabólica , Ratos , Ratos Wistar , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície , Distribuição Tecidual
Clin Exp Pharmacol Physiol ; 30(3): 153-6, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12603343


1. The aim of the present study was to understand the benefit of liposomal dry powder for inhalation (LDPI) of ketotifen fumarate (KF) over plain drug dry powder for inhalation as a pulmonary targetted drug-delivery system. 2. The KF liposomes, composed of egg phosphatidyl choline and cholesterol, were prepared by the lipid film hydration technique. The liposomal dispersion was freeze dried and formulated to a dry powder for inhalation. Values of 89.0-65.3% drug entrapment of freeze-dried liposomes were estimated in prepared batches. 3. Rehydrated KF liposomes formed by the hydration of LDPI or the plain KF solution was delivered to rat lungs by intratracheal instillation. Simultaneous monitoring of drug levels in the bronchoalveolar lavage and lung tissue enabled assessment of pulmonary drug disposition. 4. Cumulative drug levels in lung tissue after intratracheal administration revealed that with liposomes targetting factors were between 1.36 and 1.54. The maximal drug concentration in lung homogenate for LDPI was 42.0 micro g compared with 73.6 micro g for plain drug solution. 5. Similarly, the time to reach maximum drug concentration in the lung homogenate for liposomal dry powder was 9-12 h compared with 3 h for plain drug. 6. Hence, the use of LDPI of KF was found to provide desired drug levels in the lung for a long time and thereby increased pulmonary targetting 7. This is expected to enhance the therapeutic index of the drug and probably reduce the dose administered and the cost of therapy.

Cetotifeno/farmacocinética , Pulmão/metabolismo , Administração por Inalação , Animais , Química Farmacêutica , Cetotifeno/administração & dosagem , Lipossomos , Pulmão/efeitos dos fármacos , Pós , Ratos