Diclofenac partitioning into the skin is increased by the Flector Patch (Diclofenac epolamine) (1.3% w/w, 24 hours)[1]. Microemulsion (ME)-loaded Flector Patch (Diclofenac epolamine) (1.3% w/w) improves drug delivery through skin and lasts for 12 hours after ME removal[2].

Treating inflammatory disorders with Flector Patch (Diclofenac epolamine) (1.3% w/w, external application) has shown promise[2].

Animal/Disease Models: Rat paw edema inflammation model (induced with carrageenan)[2]
Doses: 1.3% w/w
Route of Administration: Exteral application
Experimental Results: Inhibited edema and demonstrated anti-inflammatory efficacy at 6 hrs (hours) after application.

Metabolism / Metabolites
Metabolized in the liver. Excretion pathway: Diclofenac is primarily metabolized and subsequently excreted in urine and bile as glucuronide and sulfate conjugates. Almost no free, unmetabolized diclofenac is excreted in urine. Approximately 65% of the dose is excreted in urine as unmetabolized diclofenac and its metabolites, and approximately 35% is excreted in bile. Half-life: 2 hours.

Toxicity Summary
Diclofenac's anti-inflammatory effects are believed to be achieved by inhibiting leukocyte migration and cyclooxygenase (COX-1 and COX-2) activity, thereby suppressing peripheral prostaglandin synthesis. Since prostaglandins sensitize pain receptors, inhibiting their synthesis is the reason for diclofenac's analgesic effect. Its antipyretic effect may stem from its action on the hypothalamus, leading to peripheral vasodilation, increased skin blood flow, and thus promoting heat dissipation.

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Effects During Pregnancy and Lactation
◉ Summary of Medication Use During Lactation
Data on diclofenac excretion in breast milk is limited, but the drug has a short half-life and produces a small amount of glucuronide metabolites. The concentration of the drug in breast milk appears to be very low. Most reviewers consider the use of diclofenac during lactation acceptable. Other medications may be preferred, especially for breastfed newborns or premature infants, as there is more publicly available information on these types of medications.
The use of diclofenac topical gel or eye drops by the mother is not expected to have any adverse effects on breastfed infants. To significantly reduce the amount of medication that enters breast milk after using eye drops, press your finger against the tear duct near the corner of the eye for at least 1 minute, then blot away any excess medication with absorbent paper towels.
◉ Effects on Breastfed Infants
In one study, 30 mothers who underwent elective cesarean sections were allowed to use 25 mg diclofenac suppositories postpartum and received spinal anesthesia or a combination of spinal-epidural anesthesia and local anesthesia. In the spinal anesthesia group, the average dose of diclofenac was 56 mg on the day of delivery and 33 mg on the second day; while women receiving combined spinal and epidural anesthesia received 21 mg and 18 mg, respectively. The study did not mention adverse reactions in breastfed infants. One breastfed infant developed urticaria on day 15 after birth. Her mother had been taking diclofenac (dosage not specified) for pain relief since her cesarean section. Diclofenac may be one of the causes of the urticaria; however, the infant had also received a hepatitis B vaccine 7 days prior, which the authors consider more likely to be the cause of the reaction. A trial in women undergoing cesarean sections randomly assigned participants to two groups: one group received two 325 mg tablets of acetaminophen and 35.5 mg of tramadol (Zaldiar, Gruenthal, Israel) every 6 hours after admission, and 100 mg of diclofenac at 12, 24, and 48 hours after admission; the other group received either a fixed dose or the same medication as needed. Results showed no difference between the two groups of newborns in terms of peak bilirubin, phototherapy requirement, and adverse reactions (including irritability or altered consciousness). No adverse reactions were observed in infants.
◉ Effects on breastfeeding and breast milk
A trial in women undergoing cesarean section randomly assigned participants to two groups. One group received two tablets of acetaminophen 325 mg and tramadol 35.5 mg (Zaldiar, Gruenthal, Israel) every 6 hours, and diclofenac 100 mg at 12, 24, and 48 hours after admission to the delivery room, using a fixed-dose regimen. The other group received the same medication as needed. Patients in the fixed-dose group breastfed more frequently (23.8 times vs. 19.2 times) and formula-fed less frequently (8.2 times vs. 11.9 times).
A randomized, double-blind study was conducted in pregnant women scheduled for cesarean section under spinal anesthesia with bupivacaine and fentanyl. Patients received 100 mg diclofenac sodium (n=100), 100 mg tramadol (n=100), or placebo (glycerin suppositories, n=100), all administered as rectal suppositories every 8 hours for 24 hours. Mothers receiving diclofenac sodium had significantly shorter times to initiate breastfeeding compared to the placebo group: 1.5 hours and 4.1 hours with breastfeeding support, and 3.5 hours and 6.2 hours without breastfeeding support, respectively. In mothers not receiving any breastfeeding support, diclofenac sodium was slightly more effective than tramadol (3.5 hours and 3.7 hours, respectively).

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Toxicity Data
LD50 = 390 mg/kg (oral administration to mice)

[1]. Topical delivery of diclofenac into and across equine skin from a novel liquid diclofenac epolamine formulation. J Vet Pharmacol Ther. 2016 Dec. 39(6):578-583.

[2]. Fouad SA, Basalious EB, El-Nabarawi MA, Tayel SA. Microemulsion and poloxamer microemulsion-based gel for sustained transdermal delivery of diclofenac epolamine using in-skin drug depot: in vitro/in vivo evaluation. Int J Pharm. 2013 Sep 10;453(2):569-78.

See also: Diclofenac (with active portion).

C20H24CL2N2O3

411.32

410.116

119623-66-4

114753

Off-white to light yellow solid powder

412ºC at 760mmHg

203ºC

1.59E-07mmHg at 25°C

4.223

3

5

6

27

363

0

C1CCN(C1)CCO.C1=CC=C(C(=C1)CC(=O)O)NC2=C(C=CC=C2Cl)Cl

DCERVXIINVUMKU-UHFFFAOYSA-N

InChI=1S/C14H11Cl2NO2.C6H13NO/c15-10-5-3-6-11(16)14(10)17-12-7-2-1-4-9(12)8-13(18)19;8-6-5-7-3-1-2-4-7/h1-7,17H,8H2,(H,18,19);8H,1-6H2

2-[2-(2,6-dichloroanilino)phenyl]acetic acid;2-pyrrolidin-1-ylethanol

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)