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Development of novel paracetamol/naproxen co-crystals with an improvement in naproxen solubility.

Co-crystals are new solid forms of drugs that could resolve more than one problem associated with drugs formulations like solubility, stability, bioavailability, mechanical and tableting properties. A preliminary theoretical study for estimating the possible bonding between the co-crystal components (paracetamol and naproxen) was performed using the ChemOffice program. The results revealed a high possibility for bonding between paracetamol and naproxen and indicated the ability of molecular mechanics study to predict the co-crystal design.

       In this work, four different methods were used for the preparation of three different ratios 1:1, 2:1, and 1:2 of paracetamol:naproxen co-crystals. The four methods are liquid-assisted grinding, solvent evaporation method, ultrasonic-assisted co-crystallization, and microwave-assisted co-crystallization. The characterization of the prepared co-crystal was performed by Fourier transform infrared spectroscopy, Thermogravimetric Analysis, Differential scanning calorimetry, Powder X-Ray diffraction, and Field emission scanning electron microscopy.

       The results showed that the most successful method for co-crystal production was solvent evaporation methods. The FTIR and DSC results indicated the formation of paracetamol-naproxen co-crystals when prepared by using the solvent evaporation method in the three ratios 1:1 (N1), 2:1 (N2), and 1:2 (N3). Moreover, the PXRD results confirm the previous conclusions.

       A solubility study was conducted to compare the water solubility of pure paracetamol and naproxen with co-crystals solubility. The naproxen solubility was improved by more than two times in (1:1) and (1:2) paracetamol/naproxen co-crystals.

       To conclude, this work succeeded in formation of new paracetamol/naproxen co-crystals, which can be considered as a new promising technique for formulation of these two drugs with an obvious enhancement in naproxen solubility and crystallinity. This could be exploited in preparation of tablets with possible enhancement in dissolution and bioavailability, however, further work is needed to prove this assumption.

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Publication Date
Sun Sep 03 2017
Journal Name
Baghdad Science Journal
Preparation and Characterization some New of Naproxen Drug Derivatives

In this research four steps of the new derivatives of Naproxen drug have been made which are known as a high medicinal effectiveness; the first step involved converting Naproxen into the corresponding ester (A) by reaction Naproxen with methanol absolute in presence H2SO4. While the second step involved treatment methyl Naproxen ester (A) with hydrazine hydrate 80% in presence of ethanol .The third reaction requires synthesis of Schiff bases (C1-C10) by condensation. of Naproxen hydrazide (B) with many substituted aromatic aldehydes . Finally, the fourth step synthesized new tetrazole derivatives ( D1- D10) by the reaction of the prepared Schiff bases (in the third step) with Sodium azide in THF as a solvent .The prepared compounds wer

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Publication Date
Thu Mar 30 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
In Situ Gelling Formulation of Naproxen for Oral Sustained Delivery System

Naproxen is non-steroidal anti-inflammatory drug, which has antipyretic and anti-inflammatory effect. It is extensively bound to plasma albumin, and exhibits gastric toxicity, so it may be more efficient to deliver the drug in its sustained release dosage form and adequate blood level is achieved. Three liquid formulations with in situ gelling properties have been assessed for their potential for the oral sustained delivery of naproxen . The formulations were dilute solutions of: (a) pectin; (b) gellan gum and; (c) sodium alginate, all containing complexed calcium ion that form gels when these ions are released in the acidic environment of the stomach . The viscosity of the sols and drug release were measured, and was found to be depende

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Publication Date
Mon Jun 25 2018
Journal Name
International Journal Of Pharmaceutical Quality Assurance
Synthesize of New Ibuprofen and Naproxen Sulphonamide Conjugate with Anti-Inflammatory Study and Molecular Docking Study

Non-steroidal anti-inflammatory drugs (NSAIDs) contain free –COOH which thought to be responsible for the GI irritation associated with all traditional NSAIDs. The esterification of this group is one of an approach to ultimate aim for reduce the gastric irritation; so in this study we synthesized and preliminarily evaluated new ester compounds as new analogues with expected selectivity toward COX-2 enzyme. Synthetic procedures have been successfully developed for the generation of the target compounds (III a and b). The synthetic approach involved multi-steps procedures which include: Synthesis of 4-hydroxy benzene sulphonamide ( I b ), synthesis of Naproxen and Ibuprofen acyl chloride and then reacting them with 4-hydroxy benzene sulphon

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Publication Date
Thu Mar 30 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Formulation and in vitro Evaluation of In-situ Gelling Liquid Suppositories for Naproxen

In-situ gelation is a process of gel formation at the site of application, in which a drug product formulation that exists as a liquid has been transformed into a gel upon contact with body fluids. As a drug delivery agent, the in-situ gel has an advantage of providing sustained release of the drug agent.  In-situ gelling liquid suppositories using poloxamer 188 (26-30% W/W) as a suppository base with 10% W/W naproxen were prepared, the gelation temperature of these preparations were measured and they were all above the physiological temperature. Additives such as polyvinylpyrrolidin "PVP" ,hydroxylpropylmethylcellulose  "HPMC", sodium alginate and sodium chloride were used in concentration ranging from (0.25-1

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Publication Date
Thu Jan 01 2015
Journal Name
Der Pharma Chemica
Synthesis, characterization and biological evaluation of new potentially active hydrazones of naproxen hydrazide

To synthesize new hydrazone derivatives of naproxen with enhanced anti-inflammatory activity and devoid the ulcerogenic side effects. Hydrazones were synthesized by conjugation of naproxen hydrazide with seven natural and synthetic aldehyde and ketone by using glacial acetic acid as catalyst. The synthesis has been carried out following simple methodology in excellent isolated yields.The structure of the synthesized derivatives has been characterized by elemental microanalysis (CHN), FTIR Spectroscopy, and other physicochemical properties.The anti- inflammatory activity of the synthesized compounds was evaluated in vivo using the egg-white induced edema model in rats, and the results of the biological assay was found to be comparable to Nap

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Publication Date
Fri Mar 31 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Micro encapsulation of Naproxen By Complex Coacervation and Aqueous Colloid Dispersion Part ( 1 )

Naproxen is a non steroidal anti inflammatory and antipyretic drug which has local irritation effect  on  the  stomach, and  unpleasant taste,  besides bad   flowability and light sensitivity .The drug was prepared as microcapsules by complex coacervation method using acacia-gelatin coating materials , and aqueous colloid polymer dispersion method ( ACPD ), using ethyl cellulose and sodium alginate coating materials . The results indicated that microcapsules prepared by 2:1  core:wall ratio is the best for both methods, with an average encapsulation efficiency (75%) and avarege yield (90%) .

Moreover the drug release was affected mainly by core : ratio ,pH enviroment and method of microenca

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Publication Date
Tue Feb 01 2022
Journal Name
Macromolecular Symposia
Synthesis of 5‐Fluorouracil–Naproxen Conjugates as a Mutual Prodrug for Targeting Cancer Tissues
Abstract<p>A new 5‐fluorouracil–naproxen conjugate is synthesized as a mutual prodrug for targeting cancer tissues. The structure of the target compound and their intermediate are characterized by their melting point, IR, <sup>1</sup>H NMR, <sup>13</sup>C NMR, and elemental microanalysis. The cytotoxic activity is preliminarily evaluated using nonsmall lung cancer CRL‐2049, human breast cancer CAL‐51, and one type of normal cell line; rat embryo fibroblast cell line. The synthesized compound shows a good cytotoxic effect at the cancer cell and no significant effect at rat embryo fibroblast cell line.</p>
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Publication Date
Thu Dec 31 2020
Journal Name
Iraqi Journal Of Market Research And Consumer Protection
SYNTHESIS OF THE NEW NAPROXEN SELECTIVE ELECTRODE BASED ON IMPRINTED POLYMER USING DIFFERENT MONOMERS AND ITS DETERMINATION AT PHARMACEUTICAL PREPARATION: SYNTHESIS OF THE NEW NAPROXEN SELECTIVE ELECTRODE BASED ON IMPRINTED POLYMER USING DIFFERENT MONOMERS AND ITS DETERMINATION AT PHARMACEUTICAL PREPARATION

ABSTRACT

Naproxen(NPX) imprinted liquid electrodes of polymers are built using polymerization precipitation. The molecularly imprinted (MIP) and non imprinted (NIP) polymers were synthesized using NPX as a template. In the polymerization precipitation involved, styrene(STY) was used as monomer, N,N-methylenediacrylamide (N,N-MDAM) as a cross-linker and benzoyl peroxide (BPO) as an initiator. The molecularly imprinted membranes and the non-imprinted membranes were prepared using acetophenone(AOPH) and di octylphathalate(DOP)as plasticizers in PVC matrix. The slopes and detection limits of the liquid electrodes ranged from)-18.1,-17.72 (mV/decade and )4.0 x 10-

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Publication Date
Fri Sep 29 2017
Journal Name
Journal Of Engineering
Studying the Improvement of the Solubility of Cellulosic Fibers

This study focuses for improving the increase the solubility of fiber cellulose in sodium hydroxide solution in concentrations ranging from (4- 12%), from one point of view and from other point of view in (sodium hydroxide and urea) solution concentration (6% NaOH + 4% urea), under  low temperature (- 15, - 20 Co) , depending on the principle of  reducing the degree of polymerization for  fiber cellulose, which is represented in our tests cotton linter who its represent  (Whatman filter paper, Grade 1), some samples subjected to chemical pretreatment as simulation the method of decomposition of cellulosic materials by white or brown fungi that grow on trees, this method involves the use of

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Publication Date
Tue Mar 28 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Synthesis and Preliminary Pharmacological Evaluation of Esters and Amides Derivatives of Naproxen as Potential Anti-Inflammatory Agents

4-chloro and 4- nitro substituted phenol and aniline incorporated to a carboxylic group of naproxen a well-known non-steroidal anti-inflammatory drug (NSAID) to increase bulkiness were synthesized for evaluation as  a potential anti-inflammatory agents with expected COX-2 selectivity. In vivo acute anti-inflammatory activity of these compounds (I-IV) was evaluated in rats using egg-white induced edema model of inflammation in a dose equivalent to (2.5 mg/Kg) of naproxen. All tested compounds produced a significant reduction in paw edema with respect to the effect of propylene glycol 50% v/v (control group). Moreover, compounds I and IV might show higher effect comparable to that of naproxen and to that of compounds II & III whic

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