Delving into the Latest Updates on Lornoxicam with Synapse

Berberine hydrochloride (BER), a promising candidate in treating tumors, diabetes and pain management, has relatively low oral absorption and bioavailability due to its low intestinal permeability. To address these challenges, we developed a BER and lornoxicam cocrystal (BLCC) by a solvent evaporation method and characterized it using X-ray diffraction, differential scanning calorimetry and thermogravimetric analysis. Compared with BER, BLCC exhibited an instant release in pH 1.0 HCl and a sustained release up to 24 h in pH 6.8 buffer solutions and water. The Caco-2 permeability of BLCC has shown a remarkable increase compared to that of BER (i.e., P_app(a→b): 50.30 × 10^-7vs 8.82 × 10^-7 cm/s), which is attributed to the improved lipophilicity of BER (i.e., log P: 1.29 vs -1.83) and the reduced efflux amount of BER (i.e., ER: 1.71 vs 12.11). Furthermore, BLCC demonstrated a relative bioavailability of 410 % in comparison to the original BER, due to notably enhanced intestinal permeability of BLCC and its continuous dissolution in simulated intestinal fluid. BLCC has the potential to tailor the dissolution behavior, improve intestinal permeability, and boost the bioavailability of BER. This indicates that the cocrystal strategy holds promise as an effective approach to improving the oral absorption and bioavailability of active pharmaceutical molecules with low permeability during drug development.

01 Oct 2024·International Journal of Biological Macromolecules

Identifying alkaline phosphatase inhibitory potential of cyclooxygenase-2 inhibitors: Insights from molecular docking, MD simulations, molecular expression analysis in MCF-7 breast cancer cell line and in vitro investigations

Article

Author: Iqbal, Ambar ; Putra, Purnawan Pontana ; Hussain, Safdar ; Ashraf, Muhammad ; Hamid, Sujhla

Alkaline phosphatases (APs, EC 3.1.3.1) belong to a superfamily of biological macromolecules that dephosphorylate many phosphometabolites and phosphoproteins and their overexpression is intricated in the spread of cancer to liver and bones, neuronal disorders including Alzheimer's disease (AD), inflammation and others. It was hypothesized that cyclooxygenase-2 (COX-2) selective inhibitors may possess anti-APs potential and may be involved in anticancer proceedings. Three COX-2 inhibitors including nimesulide, piroxicam and lornoxicam were evaluated for the inhibition of APs using in silico and in vitro methods. Molecular docking studies against tissue nonspecific alkaline phosphatase (TNAP) offered the best binding affinities for nimesulide (-11.14 kcal/mol) supported with conventional hydrogen bonding and hydrophobic interactions. MD simulations against TNAP for 200 ns and principal component analysis (PCA) reiterated the stability of ligand-receptor complexes. Molecular expression analysis of TNAP enzyme in the breast cancer cell line MCF-7 exhibited 0.24-fold downregulation with 5 μM nimesulide as compared with 0.26-fold standard 10 μM levamisole. In vitro assays against human placental AP (hPAP) displayed potent inhibitions of these drugs with IC₅₀ values of 0.52 ± 0.02 μM to 3.46 ± 0.13 μM and similar results were obtained for bovine intestinal AP (bIAP). The data when generalized collectively emphasizes that the inhibition of APs by COX-2 inhibitors provides another target to work on the development of anticancer drugs.

01 Sep 2024·Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry

Formulation and Characterization of Emulgel Lornoxicam Containing Lemon Grass Oil as Penetration Enhancer

Article

Author: Kumari, Vibha ; Bajpai, Meenakshi

Introduction:Emulgel dosage form is an advanced form of transdermal drug de-livery. It is a combination of emulsion and gel in a definite ratio. Emulsions are incorporated into the gel with proper mixing. The emulsion present in emulgel can be either oil/water or water/oil, which is thickened by mixing it with a gelling agent.Material and Methods:On the basis of the solubility of lornoxicam in various oils, a surfactant and a co-surfactant were selected for further research. For the preparation of emulgel, the emulsion was prepared with Smix (surfactant and co-surfactant) in a ratio of 1:2. The prepared emulsion was incorporated into different concentrations of carbapol 934 in a 1:1 ratio to make a homogenous emulgel.Results:The emulgel was inspected visually to see if it had any phase behaviour, spreadabil-ity, or grittiness by applying it to a slide. All formulations were evaluated for pH, physical properties, drug content, spreadability, extrudability, swelling index, viscosity, and centrifu-gation. Franz diffusion cell was used to perform in-vitro release of formulation with the help of egg membrane. Among all formulations, F3 showed 83% release after 6 hours and showed acceptable physical properties like homogeneity, colour, consistency, pH value, spreadability, extrudability, and drug content.Discussion:Thus, emulgel can be regarded as a more feasible drug delivery system for hydrophobic drugs (lornoxicam) than the currently marketed formulation. Optimized emulgel formulation consists of a microemulsion of lornoxicam, 1% of carbopol 934, propylene glycol, sodium benzoate, lemon grass oil, glycerin, and distilled water. In the in-vitro release studies, pH 7.4 phosphate buffer emulgel formulation (F3) showed 83% after 6 hours. Emulgel was found to be stable under stable conditions.Conclusion:The emulgel of the poorly water-soluble drug (lornoxicam) was formulated. The components and their optimum ratio for the formulation of microemulsion were obtained by solubility studies and droplet size analysis. Thus, microemulsion can be regarded as a more feasible dose delivery system for lornoxicam than the currently marketed tablet, capsule, and injection formulations. Optimized microemulsion of lornoxicam was incorporated into the gel base. Therefore, it may be concluded that emulgel of lornoxicam can be used as a controlled-release dosage form of the drug for local application in rheumatoid arthritis.

100 Deals associated with Lornoxicam

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External Link

KEGG	Wiki	ATC	Drug Bank
D01866	Lornoxicam	M01AC05	DB06725

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Rheumatic Diseases	JP	Takeda Pharmaceuticals International AG	20 Jun 2001
Bursitis	JP	Taisho Pharmaceutical Co., Ltd.	02 Feb 2001
Cervicobrachial syndrome	DK	-	01 Jan 1997
Low Back Pain	DK	-	01 Jan 1997
Neuralgia	DK	-	01 Jan 1997
Osteoarthritis	DK	-	01 Jan 1997
Pain, Postoperative	DK	-	01 Jan 1997
Periarthritis	DK	-	01 Jan 1997
Rheumatoid Arthritis	DK	-	01 Jan 1997

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Headache	Discovery	US	POZEN, Inc.	01 Dec 2005
Migraine Disorders	Discovery	US	POZEN, Inc.	01 Dec 2005
Pain, Postoperative	Discovery	US	POZEN, Inc.	01 Nov 2005

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Clinical Result

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Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01117948 (CTgov)	Phase 2	Alzheimer Disease	219	Lornoxicam (Lornoxicam)	njaohvfpmu(aggjaoiyhp) = fmwtgsreks kmksefrfpm (szrverqzuc, jgbjzbcylg - yxapxjsfmo) View more	-	29 Nov 2012
				Placebo (Placebo)	njaohvfpmu(aggjaoiyhp) = irafphcife kmksefrfpm (szrverqzuc, rhyqekqlng - efuxeixena) View more