Ulcerogenic Properties Research Articles

Insights into Prospects of Novel NSAID Prodrugs in the Management of Gastrointestinal Toxicity: A Perspective Review.

Non-steroidal anti-inflammatory drugs (NSAIDs) have a long history in the healthcare system due to their therapeutic potential. These NSAIDs cause ulcerogenicity, stomach pains, gastrointestinal hemorrhage, mucosa bleeding, and pancreatitis when used moderately and consistently. With researchers, managing the aforementioned adverse effects therapeutically is getting increasingly difficult. One method for creating NSAID moieties with low penetration as well as ulcerogenic properties is the prodrug technique. During the oral consumption of NSAID-prodrugs, ulcerations, intestinal hemorrhage, and mucosa hemorrhage have significantly decreased. Considering this background, this review focussed on NSAID prodrugs as well as their justifications, the pathogenesis of NSAIDs inducing gastrointestinal toxicity, and the role of different antioxidants and spacer groups. Prodrug moieties have more advantages over parent medicines concerning both solubility and lipophilicity. In general, NSAID-class prodrugs can successfully treat both acute and long-term inflammation and aches without causing ulcerotoxicity and related gastrointestinal side effects, which reduces their burden from the pharmacoeconomic perspective.

DENTAL USE OF KETOROLAC TROMETHAMINE: STATUS AND FUTURE PERSPECTIVES

The history of evidence-based use of non-steroidal anti-inflammatory drugs (NSAIDs) goes back at least two hundred and fifty years. Over the past period, the path has been passed from the use of willow bark decoctions to the synthesis and introduction of selective cyclooxygenase inhibitors into clinical practice. To date, the research direction has shifted from the search for new substances to the search for new routes of administration. The wide range of existing drug substances, however, has only in a few dosage forms. Thus, ketorolac tromethamine is known only as a solution for parenteral and intranasal administration, as well as oral tablets. This drug belongs to NSAIDs, particularly non-selective cyclooxygenase inhibitors, and shows a pronounced analgesic activity. Due to this property, ketorolac can serve as an alternative to opioid analgesics or can reduce the dosage of the latter when used in combination. However, a number of systemic side effects (ulcerogenic properties, negative effect on the blood), unfortunately, impose their limitations. A possible solution to this situation may be the creation of local delivery systems, in particular, in situ implants. This review highlights the problem of developing local systems for the delivery of ketorolac tromethamine for the relief of acute pain. Special attention is paid to in situ implants based on bioadhesive polymers.

Synthesis, anti-inflammatory properties, molecular modelling and potential COX-2, TNF-α, PGE2 and IL1β inhibitors of pyrazole-based scaffolds

Starting from the precursors 3-(4-methoxyphenyl)-1H-pyrazole-4-carbaldehyde (1) and 3-(4-bromophenyl)-1-ethyl-1H-pyrazole-4-carbaldehyde (2), a variety of trisubstituted pyrazole derivatives 3-15 were synthesized and evaluated for their anti-inflammatory, analgesic, antipyretic and ulcerogenic properties. Derivatives 3a, 3b, 6, 8 and 11 showed promising anti-inflammatory observations with potencies of 99.5, 100.3, 92.4, 77.1 and 103.1, respectively, compared with celecoxib the used standard reference, they also exhibited a promising onset action of analgesic with efficiency superior to the used reference drug, in addition to their antipyretic effect and safety margin for gastric mucosa compared with the reference drugs. Based on the obtained observations, derivatives 3a, 3b, 6, 8 and 11 were assayed for their COX-2, TNF-α, PGE2 and IL1β levels in rat paws using the carrageenan inflammation model with the ELISA kit. Compound 8 has the best promising anti-inflammatory observations, antipyretic effect and long-lasting analgesic activity without ulcerogenic potential in addition to showing mutual inhibitory effects on all tested enzymes. Furthermore, a molecular docking study was introduced to recognize the binding interactions of the most potent candidates 3a, 3b, 6, 8 and 11 into the active sites of COX-2 and TNF-α. Compound 8 has the best binding interaction scores with both targeted enzymes that supported its obtained bio-observations and prove that it has the potential to be developed into an anti-inflammatory drug.

Design and synthesis of ibuprofen-quinoline conjugates as potential anti-inflammatory and analgesic drug candidates

A new set of ibuprofen-quinoline conjugates comprising quinolinyl heterocycle and ibuprofen moieties linked by an alkyl chain were synthesized in good yields utilizing an optimized reaction procedure in a molecular hybridization approach to overcome the drawbacks of the current non-steroidal anti-inflammatory drugs. The synthesized conjugates were screened for their anti-inflammatory, and ulcerogenic properties. Several conjugates were found to have significant anti-inflammatory properties in the carrageenan-induced rat paw edema test without showing any ulcerogenic liability. In addition, most conjugates showed promising peripheral analgesic activity in the acetic acid-induced writhing test as well as central analgesic properties in the in vivo hot plate test. The most promising conjugates were the unsubstituted and 6-substituted fluoro- and chloro-derivatives of 2-(trifluoromethyl)quinoline linked to ibuprofen by a propyl chain. Their anti-inflammatory activity was evaluated against LPS-stimulated inflammatory reactions in RAW264.7 mouse macrophages. In this regard, it was found that most of the conjugates were able to significantly reduce the release and production of nitric oxide in the LPS-stimulated macrophages. The secretion and expression of the pro-inflammatory cytokines IL-6, TNF-α, and inducible nitric oxide synthase (iNOS) were also significantly suppressed.

Formulation Design and <i>in vitro-in vivo</i> Evaluation of Sustained Release Aspirin Microparticles Based on PEGylated Lipids

Background: PEGylation is a strategy that on therapeutic molecules such as drugs, proteins and macromolecules, in order to improve their delivery. It has this unique property of increasing the size and molecular weight of biomolecules that are conjugated in nature in order to improve water solubility, reduction in renal clearance and protects the drug from enzymatic degradation. Objectives: The objectives of this work was to formulate sustained release aspirin-loaded solid lipid microparticles based on PEGylated lipid matrix, to evaluate the <i>in-vitro</i> properties of the SLM and to study the anti-inflammatory and ulcerogenic properties of the SLM. Methods: Aspirin-loaded solid lipid microparticles (SLMs) were formulated by cold homogenization method. Furthermore, they were analyzed for the encapsulation efficiency, <i>in-vitro</i> release, particle size, anti-inflammatory and ulcer inhibition properties. Results: Particle size ranged from 9.36±2.63 to 16.77±5.80 µm for batches B₁ to D₁ SLMs loaded with 10% LM, 5% PEG 4000 and 0.25-1% aspirin respectively, while batches B₂ to D₂ formulated with 10% LM, 10% PEG and 0.25 -1% aspirin had particle size range of 9.09±4.03 to 15.71±10.09 µm. Batches D₁ containing 1% of aspirin had the highest encapsulation efficiency of 58%. Maximum <i>in-vitro</i> release of 29.20% and 15.85% were obtained at 6 h for batches D₁ and B₂ respectively. SLMs showed an average of 66.67 – 83.3% oedema inhibition, while the reference had 50%, and ulcer inhibition of 75% for batch D₁. Conclusion: Due to the good properties exhibited by the aspirin-loaded SLMS, they could be used for the treatment of inflammation.

Synthesis of new ibuprofen hybrid conjugates as potential anti-inflammatory and analgesic agents.

Background: A new set of hybrid conjugates derived from 2-(4-isobutylphenyl)propanoic acid (ibuprofen) is synthesized to overcome the drawbacks of the current non-steroidal anti-inflammatory drugs. Results &methodology: Synthesized conjugates were screened for their anti-inflammatory, analgesic and ulcerogenic properties. Few conjugates were found to have significant anti-inflammatory properties in the carrageenan-induced rat paw edema test, while a fair number of conjugates showed promising peripheral analgesic activity in the acetic acid-induced writhing test as well as central analgesic properties in the in vivo hot plate technique. The newly synthesized conjugates did not display any ulcerogenic liability. Conclusion:In vitro, COX-1 and COX-2 enzyme inhibition studies raveled compound 7e is more selective toward COX-2 compared with ibuprofen.

Gastroulcerogenic Evaluation of Ibuprofen Ester Conjugates

The aim of this study is to search for any potential gastric ulcerogenic properties of the ester form of ibuprofen in comparison with Ibuprofen in order to establish the gastrointestinal safety profile. Ibuprofen ester derivates were synthesized and were tested for their gastroulcerogenic side effects. The esterification of ibuprofen suppressed its gastric ulceration which is associated with its side effect as an antiinflammation. Research results showed that the rat group given Ibuprofen ester conjugate compound had fewer ulcers, smaller ulcer diameters, and less severe ulcer onditions. Histological examination showed that rat in the group given Ibuprofen ester conjugates had lesser number of hemorrhage and congestion compared to the group given ibuprofen. In conclusion, the treatment of Ibuprofen ester conjugates has a lower risk of ulcerogenic effects than the treatment of ibuprofen.

Synthesis and Pharmacological Activity of S(-)-2-Amino-2-Methyl-3-Phenylpropanoic Acid

Taking into account the high efficacy of 2-arylpropionic acid derivatives among NSAIDs and based on their SARs, we have evaluated the anti-inflammatory, antinociceptive, and antiaggregant activity and ulcerogenic properties of a new synthesized non-protein amino acid (NPAA) derivative S(-)-2-amino-2-methyl-3-phenylpropanoic acid (NPAA-36). A new method of NPAA-36 synthesis was developed and experiments were carried out, which showed that this compound injected in a dose of 10 mg/kg (i.p.) inhibited xylene-induced ear oedema by about 31.1%, which proved its anti-inflammatory properties. The antinociceptive activity of NPAA-36 was assessed in tail-flick test by the ability to increase the tail cut-off latency by 36.78% within 60 min after injection at the same dose. Investigation of the ulcerogenic properties of NPAA-36 demonstrated that it exhibited lower gastrointestinal toxicity than a well-known arylpropionic acid derivative NSAID. Results of in vitro experiments showed the antiplatelet activity registered not in all (only in 41.2%) cases, which might imply lower bleeding. The obtained data indicate that the new NPAAderivative can be a potential basis for the development of new anti-inflammatory drugs with weak side effects.

Synthesis of some new thiazolo[4,5-b]pyridin-2-ones and research of their anti-inflammatory activity

In modern theoretical and clinical medicine inflammation problem remains one of the main.Deregulation of inflammatory processes leads to specific pathologies.There is a significant amount of drugs used to treat inflammation. But all of them have varying degrees of ulcerogenic properties. To overcome these limitations search is ongoing throughout the World to find new effective and safe anti-inflammatory agent. Therefore, of course, the synthesis of thiazolidines annelated with the pyridine cycle and the study of their anti-inflammatory properties is an interesting and relevant area.&#x0D; The objective of the present work was to synthesize a series of novel thiazolo[4,5-b]pyridine-2-ones by the structural modification of the (5,7-dimethyl-2-oxo-thiazolo[4,5-b]pyridine-3-yl)-acetic acid hydrazide for further pharmacological screening in vivo as anti-inflammatory activities.&#x0D; The objects of the study were thiazolo[4,5-b]pyridines, obtained by the structural modification of the (5,7-dimethyl-2-oxo-thiazolo[4,5-b]pyridine-3-yl)-acetic acid hydrazide. Anti-inflammatory activity was evaluated using carrageenan induced rat paw edema method in rats&#x0D; In vivo studies were carried out for anti-inflammatory activity employing the carrageenan-induced rat paw edema method. Anti-inflammatory activity was defined by measuring the paw edema volume 4 h after the carrageenan injection.The NSAID drug Ibuprofen in effective therapeutic doses were tested inparallel as an activity references. Inhibition of the inflammatory response was expressed as a percentage of the paw volume reduction. Studies of anti-inflammatory activity showed that the synthesized compounds had pronounced diuretic properties, and some of them according to activity indicators were approaching or exceeding comparative preparations.&#x0D; The results of the anti-inflammatory activity of the synthesized compounds derivatives (5,7-dimethyl-2-oxo-thiazolo[4,5-b]pyridine-3-yl)-acetic acid hydrazide show the potential for the search for anti-inflammatory agents among thiazolo[4,5-b]pyridine-2-ones.

Pyrido[1,2‐a]pyrimidin‐4‐ones: Ligand‐based Design, Synthesis, and Evaluation as an Anti‐inflammatory Agent

In the present study, a series of novel pyrido[1,2‐a]pyrimidin‐4‐one derivatives (1–45) were synthesized, characterized, and evaluated for their anti‐inflammatory activity. The structures of all newly synthesized compounds were confirmed by 1H NMR, 13C NMR, mass spectroscopy, and C, H, and N analyses. Preliminary these newly synthesized compounds were evaluated for their in vitro cyclooxygenase (COX)‐2/COX‐1 inhibitory activity. The celecoxib, a COX‐2 inhibitor, was used as a reference standard drug. In this inhibitory study, compounds 42, 43, 44, and 45 were found to have significant in vitro inhibitory profile as compared with the reference drug. These compounds were then subjected to their in vivo anti‐inflammatory assay by using carrageenan‐induced rat paw edema method in next level of screening. Later, these same compounds were tested for their ulcerogenic property. Based on these activity data, the compound 43 (in vitro COX‐2 activity—IC50 = 0.4 μM, SI = 400, in vivo anti‐inflammatory activity—72% inhibition after 3 h, and 0.38%—Ulcer index) was emerged as most promising anti‐inflammatory agent with very low ulcerogenic action.

Design and Synthesis of 1,2,4-Triazolo[3,2-b]-1,3,5-thiadiazine Derivatives as a Novel Template for Analgesic/Anti-Inflammatory Activity.

Previously, we demonstrated that certain heterocyclic compounds derived from 3-substituted-1,2,4-triazole-5-thiones had promising analgesic/anti-inflammatory activities together with low ulcerogenic properties. Therefore, we sought to design and synthesize new derivatives of triazol-5-thiones-fused heterocycles. In the present study, a series of novel bis-Mannich bases, namely 2,6-disubstituted-6,7-dihydro-5H-1,2,4-triazolo[3,2-b]-1,3,5-thiadiazines (1a-d, 2a-c, and 3a-d), were synthesized and characterized to assess their possible anti-inflammatory/analgesic properties. Additionally, their ability to induce gastric toxicity was also evaluated. Several of the condensed compounds produced a degree of analgesic activity comparable to reference drugs in both the hot plate and tail-flick tests. A strong anti-inflammatory effect was observed for the derivatives carrying a benzyl group at the second position (2a-c). The majority of the prepared compounds caused comparatively less gastrointestinal (GI) side effects than the reference drugs naproxen and indomethacin did. These results showed that 1,2,4-triazolo[3,2-b]-1,3,5-thiadiazine derivatives might afford a safer alternative to currently available analgesic/anti-inflammatory agents for the treatment and management of inflammatory disease and pain.

Chemical Modifications of Ketoprofen (NSAID) in Search of Better Lead Compounds: A Review of Literature From 2004-2016.

Ketoprofen, a potent anti-inflammatory, analgesic and anti-pyretic drug belonging to the propionic acid class was synthesized in 1968. Rapid absorption, simple metabolism, faster blood brain barrier crossing and high antinociceptive activity are the features responsible for its high use. But, free acidic moiety present in its structure is the major factor that declines its popularity by causing various gastric side effects. Many researchers have chemically modified this drug with the aim to discover an improved and safe NSAID candidate or a new drug with altered activity. We thoroughly searched the literature and found that during the period 2004-2016, more than fifty reports are available on chemical modification of ketoprofen. Along with this, many patents involving chemical modification of ketoprofen have also been reported. However, it was very surprising to note that there are only a few review articles available covering only its pharmacological and clinical properties. There is no review article available covering the chemistry part of ketoprofen. This motivated us to compile the information available on ketoprofen and its derivatives. The purpose of this article is to present an updated review about this topic. We thoroughly searched the peer reviewed research literature and compiled all such reportings (2004 onwards) for the benefit of researchers who further want to work on ketoprofen or other NSAIDs. Studies have been conducted to invent strategies to reduce the ulcerogenic properties of ketoprofen and in the course of time, its modified and improved derivatives have been synthesized in search of safer NSAIDs. Along with the aim of reducing the gastric side-effects, researchers have also done chemical modifications in the structure of ketoprofen to improve its solubility, to alter its blood brain-barrierr permeability, to improve its pharmacodynamic profile and to get derivatives possessing antioxidant, antiviral, anticancer and immunomodulatory activities. The findings of the review confirm that chemical modifications of ketoprofen decrease ulcer producing side effect while maintaining its desirable actions. Some derivatives were also found to possess better activity profile compared to the parent drug.

2-Aminobenzimidazole conjugates of NSAIDS: novel compounds with immunomodulatory, anti-inflammatory and antioxidant actions

2-Aminobenzimidazole (ABZ) and guanidine have immunomodulatory activity, whereas NSAIDs have anti-inflammatory activity. We, therefore, developed several novel ABZ-NSAID conjugate compounds and tested their anti-inflammatory and immunomodulatory activities. We also measured their antioxidant and ulcerogenic properties. We found that all compounds had not only anti-inflammatory activity but they also had immunomodulatory and antioxidant activities. While compound 2 had immunostimulatory activity (humoral antibody titre, HAT 7.2 ± 0.20 and carbon clearance index, K 0.030 ± 0.001), compound 9 had immunosuppressive activity (HAT 3.4 ± 0.24 and K 0.012 ± 0.002). These two compounds did not produce ulcers and hence were safe to the gastric mucosa. In addition, we used Lipinski’s parameters and found that all compounds had drug-like properties. Thus, we have provided new evidences to use compounds 2 and 9 for the treatment of inflammatory and immunomodulatory disorders like rheumatoid arthritis, ulcerative colitis, multiple sclerosis, osteoarthritis and cancer.

Anti-inflammatory, antinociceptive and ulcerogenic properties of indomethacin tablets based on solidified reverse micellar solution (SRMS)

The aim of the present study was to evaluate in vivo the anti-inflammatory, antinociceptive and ulcerogenic properties of indomethacin tablets based on solidified reverse micellar solution (SRMS). SRMS consisting of mixtures of phospholipid (Phospholipon® 90H) and triglyceride (Softisan® 154) were prepared in the ratios of 1:1, 2:1 and 1:2, respectively. SRMS based tablets containing 75 mg of indomethacin each were prepared using validated plastic mould. The physicochemical properties of the tablet formulations were studied using both official and unofficial tests. Anti-inflammatory, analgesic/antinociceptive and ulcerogenic properties of indomethacin tablets based on SRMS were studied. The results showed that the physicochemical properties of the tablet formulations were significantly affected by the composition/ratio of the lipid matrix used. The softening time in SIF ranged from 53.7 ± 0.5 to 102.6 ± 0.5 min. Results of analgesic/antinociceptive properties showed that indomethacin tablets formulated with the SRMS 1:1 had an increase in pain reaction time at 7 h significantly (p < 0.05) different from the results exhibited by tablets formulated with the lipid matrices, SRMS 1:2 and 2:1 and the reference, which showed a decrease in pain reaction time at 7 h. Indomethacin tablets based on SRMS had good anti-inflammatory properties and also inhibited the ulcerogenicity of indomethacin by 70 to 80%. Therefore, indomethacin tablets based on SRMS could be used for improved oral bioavailability of indomethacin and to enhance patient’s compliance due to inhibition of gastric irritation effect of this drug. Key words: Non steroidal anti-inflammatory drugs (NSAIDS), solidified reverse micellar solutions (SRMS), tablets, ulcerogenicity, antinociception, lipids.

Comparative evaluation of gastroulcerogenic potential of nitrogen isoforms of salicyl alcohol and aspirin in rats: biochemical and histological study

The aim of the current study was to explore in vivo any relative gastroulcerogenic prospective propensity of newly synthesized nitrogen containing derivatives of salicyl alcohol; compound (I) [1-(2-hydroxybenzyl)piperidinium chloride], compound (II) [4-carbamoyl-1-(2-hydroxybenzyl)piperidinium chloride] and aspirin in albino rats. The experimental groups received the following oral treatments daily for 6 days: group I saline control; group II, standard (aspirin) treatment group [150 mg/kg of body weight]; group III, test (compound I) treatment group [100, 150 mg/kg]; group IV, test (compound II) treatment group [100, 150 mg/kg]. The results showed that in the case of the aspirin treated group and compound (I) [150 mg/kg], there was a significant increase in gastric volume, free acidity, total acidity, ulcer score and a decrease in gastric pH. Furthermore, histopathological examination of gastric mucosa of these treated groups revealed detectable morphological changes. Utilizing the same protocol, synthetic compound (I) [100 mg/kg] and (II) [100, 150 mg/kg] exhibited no statistically significant ulcerogenic or cytotoxic properties. A cyclooxygenase (COX) selectivity test indicated the preferential inhibition of COX-I and COX-II enzymes by compounds (I) and (II). This study therefore indicates that these synthetic compounds may possess reduced ulcerogenic potential and could be a functional substitute to aspirin.

Novel ibuprofen prodrugs with improved pharmacokinetics and non-ulcerogenic potential

In the present study, we evaluated the anti-inflammatory activity with pharmacokinetic, ulcerogenic properties of various synthesized prodrugs of ibuprofen in experimental animals. Prodrugs 2, 6, 9, 10, 12, and 14 were found to possess significant anti-inflammatory activity with almost non-ulcerogenic potential than standard drug ibuprofen 1a in both normal and inflammation-induced rats. Metabolic stability of prodrugs 2, 6, 9, 10, 12, and 14 were also studied in rat liver microsomes and oral bioavailability was determined by estimating area under curve (AUC) and plasma concentration of these prodrugs at various time intervals. The experimental findings elicited higher AUC and plasma concentration at 1 and 2 h indicating improved oral bioavailability as compared to parent ibuprofen. These prodrugs are found to have least gastric ulceration with retain anti-inflammatory activity observed in experimental animals. Therefore, present experimental findings demonstrated significant improvement of various pharmacokinetic properties with least ulcerogenic potential of ester prodrugs of ibuprofen an anti-inflammatory agent

&lt;i&gt;In vitro&lt;/i&gt; and &lt;i&gt;In vivo&lt;/i&gt; Characterisation of Piroxicam-Loaded Dika Wax Lipospheres

Purpose: To formulate piroxicam-loaded lipospheres and evaluate their in vitro and in vivo properties.Method: Piroxicam-loaded lipospheres were prepared by hot homogenization technique using dika wax and Phospholipon® 90G (1:1, 1:2 and 2:1) as the lipid matrix. Characterisation, based on particle sizeand morphology, pH, drug content and encapsulation efficiency, were carried out on the lipospheres. In vitro release was evaluated in simulated intestinal fluid (pH 7.5). Anti-inflammatory and ulcerogenic properties of the piroxicam-loaded lipospheres were studied using healthy, adult Wistar rats.Result: Photomicrographs revealed spherical particles in the range of 1.66 – 3.56 ìm. The results also indicated that lipospheres formulated with lipid matrix 1:1 and containing 0.25 % piroxicam had the highest encapsulation efficiency of 84 %. In vitro release data showed that lipospheres formulated with lipid matrix having higher concentration of dika wax exhibited the fastest drug release of drug with maximum release time between 60 - 70 min. The lipospheres exhibited good anti-inflammatoryproperties with 58.6 % oedema inhibition at 5 h. Piroxicam-loaded liposheres had an ulcer index of zero while, the reference (plain piroxicam) had an ulcer index of 15.00 ± 1.23 (p &lt; 0.05).Conclusion: Piroxicam lipospheres formulated with a mixture of dika wax and phospholipid exhibited good in vitro and in vivo properties.Keywords: Dika wax, Lipospheres, Piroxicam, Phospholipid, Ulcerogenicity, Anti-inflammatory

Formulation, in vitro and in vivo Characterisation of Diclofenac Potassium Sustained Release Tablets Based on Solidified Reverse Micellar Solution (SRMS)

Aims: To formulate sustained release diclofenac potassium tablets based on solidified reverse micellar solution (SRMS) and to evaluate the in vitro and in vivo properties of the tablets. Study Design: Formulation, in vitro and in vivo evaluation of sustained release diclofenac potassium. Place and Duration of Study: Department of Pharmaceutical Technology and Industrial Pharmacy, University of Nigeria, Nsukka and Department of Pharmaceutics, University of Nigeria, Nsukka 410001, Nigeria. Methodology: SRMS, consisting of mixtures of phospholipid and triglyceride were prepared in the ratios of 1:1, 2:1 and 1:2 (Phospholipon® 90H: Softisan® 154) respectively. SRMS-based tablets containing 100 mg of diclofenac potassium each were prepared using validated plastic mould. The physicochemical properties of the tablet formulations were studied and compared with the market brands of the drug for sustained release properties. In vitro release was carried out in simulated intestinal fluid (SIF, pH 7.5) using the USP paddle method. Anti-inflammatory, analgesic/anti-nociceptive and ulcerogenic properties of the formulated tablets were studied using adult Wistar rats. Results: The results showed that the physicochemical properties of the tablet formulations were significantly affected by the composition/ratio of the lipid matrix (LM) used (p < 0.05). The hardness of the tablets ranged from 4.55 ± 0.50 to 5.10 ± 0.39 kgf for tablets formulated with LM 1:2 and 1:1 (M3 and M1) respectively. Friability results indicated that all the SRMs tablets exhibited friability values less than 1 %. The erosion time ranged from 35.8 ± 1.10 to 120.3 ± 0.32 min. The release profile of the tablets showed maximum release between 8 – 11 h for all the batches. Diclofenac potassium tablets based on SRMS had good anti-inflammatory and analgesic properties and also inhibited the ulcerogenicity of the NSAID by up to 85 %. Conclusion: Diclofenac potassium tablets based on SRMS could be used for once daily administration.

Formulation, in vitro and in vivo Characterisation of Diclofenac Potassium Sustained Release Tablets Based on Solidified Reverse Micellar Solution (SRMS)

Aims: To formulate sustained release diclofenac potassium tablets based on solidified reverse micellar solution (SRMS) and to evaluate the in vitro and in vivo properties of the tablets. Study Design: Formulation, in vitro and in vivo evaluation of sustained release diclofenac potassium. Place and Duration of Study: Department of Pharmaceutical Technology and Industrial Pharmacy, University of Nigeria, Nsukka and Department of Pharmaceutics, University of Nigeria, Nsukka 410001, Nigeria. Methodology: SRMS, consisting of mixtures of phospholipid and triglyceride were prepared in the ratios of 1:1, 2:1 and 1:2 (Phospholipon® 90H: Softisan® 154) respectively. SRMS-based tablets containing 100 mg of diclofenac potassium each were prepared using validated plastic mould. The physicochemical properties of the tablet formulations were studied and compared with the market brands of the drug for sustained release properties. In vitro release was carried out in simulated intestinal fluid (SIF, pH 7.5) using the USP paddle method. Anti-inflammatory, analgesic/anti-nociceptive and ulcerogenic properties of the formulated tablets were studied using adult Wistar rats. Results: The results showed that the physicochemical properties of the tablet formulations were significantly affected by the composition/ratio of the lipid matrix (LM) used (p &lt; 0.05). The hardness of the tablets ranged from 4.55 ± 0.50 to 5.10 ± 0.39 kgf for tablets formulated with LM 1:2 and 1:1 (M3 and M1) respectively. Friability results indicated that all the SRMs tablets exhibited friability values less than 1 %. The erosion time ranged from 35.8 ± 1.10 to 120.3 ± 0.32 min. The release profile of the tablets showed maximum release between 8 – 11 h for all the batches. Diclofenac potassium tablets based on SRMS had good anti-inflammatory and analgesic properties and also inhibited the ulcerogenicity of the NSAID by up to 85 %. Conclusion: Diclofenac potassium tablets based on SRMS could be used for once daily administration.

Synthesis and anti-inflammatory activity of novel pyridazine and pyridazinone derivatives as non-ulcerogenic agents

Herein, we report the synthesis and pharmacological properties of several series of pyridazine and pyridazinone derivatives. All the synthesized compounds were tested, in vivo, for their anti-inflammatory and ulcerogenic properties against indomethacin, as a reference compound. Compounds 4a and 9d have shown a potent anti-inflammatory activity more than indomethacin with rapid onset of action and safe gastric profile. The latter compounds were then selected for further investigation. In the MTT assay in vitro, both compounds were identified as potent and selective COX-2 inhibitors.