• New Ph. Eur. reference standards and Replacement batches for Ph. Eur. reference standards
• Distribution quota
• Removal
• Future removal
• Change of sales units
• Information on change of amount per unit
• Information on change of price
• Change of EDQM storage/shipping conditions
• Information on International Chemical Reference Substances (ICRS) and International Standards for Antibiotics (ISA)
• Rules about Substances depleting the ozone layer

See also:

With competitive price and timely delivery, Jiayi Pharmaceutical sincerely hope to be your supplier and partner.

• Content of the Ph. Eur. RS catalogue
• How to place an RS order
• The EDQM helps the users to test some draft texts proposed in Pharmeuropa through Qualified Samples

The European Directorate for the Quality of Medicines & HealthCare (EDQM) announces the release of:

• 7 new European Pharmacopoeia (Ph. Eur.) reference standards:

Catalogue code

Name

Unit quantity

Price

Y

Ciprofibrate for system suitability B CRS

2.03 mg

79 EUR

Y

Erlotinib impurity mixture CRS

0.002 mg

79 EUR

Y

Chloroxylenol for system suitability CRS

55 mg

79 EUR

Y

Haloperidol decanoate impurity mixture CRS

0.08 mg

79 EUR

Y

Colchicine for system suitability B CRS

10 mg

79 EUR

Y

Lercanidipine hydrochloride CRS

90 mg

300 EUR

Y

Rhodiola root and rhizome dry extract for system suitability HRS

60 mg

79 EUR

• 17 replacement batches for Ph. Eur. reference standards:

Catalogue code

Name

Batch

Unit quantity

Price

Y

Etonogestrel impurity mixture CRS

2

100 µL

79 EUR

Y

Ginkgolic acids CRS

4

50 mg

79 EUR

Y

Nimesulide for peak identification CRS

4

10 mg

79 EUR

D

Dihydroergocristine mesilate CRS

4

120 mg

79 EUR

D

Dimenhydrinate CRS

2

50 mg

79 EUR

Y

Epinastine for system suitability A CRS

2

10 mg

79 EUR

Y

Eplerenone for peak identification CRS

2

10 mg

79 EUR

Y

Erythropoietin for physicochemical tests CRS

2

16 mg

170 EUR

Y

Fluocinolone acetonide for system suitability CRS

2

15 mg

79 EUR

Y

For more information, please visit Praziquantel Ep Standard.

Pemetrexed disodium heptahydrate CRS

3

200 mg

79 EUR

B

Biperiden hydrochloride CRS

2

60 mg

79 EUR

R

Reserpine CRS

4

100 mg

79 EUR

Y

Bupivacaine impurity E CRS

5

20 mg

79 EUR

Y

Equilin CRS

2

20 mg

79 EUR

P

Penicillamine CRS

2

100 mg

79 EUR

C

Chlorhexidine CRS

6

50 mg

79 EUR

P

Praziquantel CRS

5

200 mg

79 EUR

• Distribution quota

Information on distribution quota for Immunoglobulin (anti-A, anti-B antibodies test Negative control) BRP (Y)

Due to premature depletion of stocks of the Immunoglobulin (anti-A, anti-B antibodies test Negative control) BRP (cat. # Y), we wish to inform users that a tight distribution quota has been established.

This BRP will be distributed to plasma-derived therapeutic product manufacturers and Official Medicines Control Laboratories only, with a maximum of 1 unit per month. This quota may be adjusted according to availability.

This exceptional measure will remain in place until the next batch of this BRP is established, which is expected by the end of .

Distribution of the Immunoglobulin for anti-A, anti-B antibodies limit test BRP (cat. # Y) and the Immunoglobulin (anti-A, anti-B antibodies test Positive control) BRP (cat. # Y) is not affected by this measure.

We apologise for any inconvenience caused and thank you for your understanding.

Information on reference standards removed from catalogue

• Supplement 11.3

Following the implementation of Supplement 11.3, the following standards are officially withdrawn (or replaced) from 1 January .

Information on reference standards with a future removal from catalogue

• Supplement 11.4

Following the implementation of Supplement 11.4, the following standards will be officially withdrawn (or replaced) from 1st April .

• Supplement 11.5

Following the implementation of Supplement 11.5, the following standard will be officially withdrawn (or replaced) from 1st July .

• Additional removal from catalogue

Information on change of sales units

• The sales unit of Erythropoietin for physicochemical tests CRS (Y) has been changed from 3 to 1 unit. The quantity per vial is sufficient to perform the test mentioned in Ph. Eur. monograph .

Information on change of amount per unit

• Equilin CRS (Y) batch 2 contains 20mg per unit (15 mg previously)
• Fluocinolone acetonide for system suitability CRS (Y) batch 2 contains 15mg per unit (10 mg previously)
• Erythropoietin for physicochemical tests CRS (Y) batch 2 contains 16mg per unit (0.1 mg previously)
• Dihydroergocristine mesilate CRS (D) batch 4 contains 120mg per unit (250 mg previously)
• Dimenhydrinate CRS (D) batch 2 contains 50mg per unit (100 mg previously)

Information on change of price

• None

Information on change of EDQM storage/shipping conditions

Based on new stability information, storage and shipping conditions will be changed on 15 April for the following reference standard:

• Atorvastatin for peak identification B (Y) CRS batch 1 is stored at -20°C (previously +5°C) and shipped on ice at -20°C (previously ambiant).

Information on International Chemical Reference Substances (ICRS) and International Standards for Antibiotics (ISA)

ICRS

• None

ISA

• None

Rules about substances depleting the ozone layer

Regulation (EU) /590 on substances that deplete the ozone layer entered into force on 11 March . The rules governing the placing on the market and use of ozone-depleting substances for essential laboratory and analytical uses have now changed.

Under the new regulation, standards shipped to a location within the European Union no longer need to be registered in the labODS registry.

There is no change to the procedure for shipments outside the European Union.

The EDQM Reference Standards affected by this change are:

R

Class 1 residual solvent solution CRS

T

Trichlorotrifluoroethane CRS

Important notes:

In all cases, these Reference Standards supplied by the EDQM must be used exclusively for essential laboratory and analytical uses (i.e. for analytical uses in conjunction with the texts published in the European Pharmacopoeia).

We would also like to draw your attention to the obligations of users affected by this change that are described under Article 8(4) of this regulation.

Content of the European Pharmacopoeia RS catalogue

The EDQM proposes more than 3 100 Ph. Eur. RS including a wide range of highly characterised chemical reference substances (CRS), herbal reference standards (HRS) and biological reference preparations (BRP), as well as reference spectra for the tests and assays to be carried out in accordance with the official methods prescribed in the Ph. Eur.

The Ph. Eur. RS catalogue is updated on a daily basis and gives access not only to all the Ph. Eur. RS, but also to:

• batch validity statements (BVSs) for each reference standard;
• Safety Data Sheets and Safety Data Statements for hazardous biologicals;
• leaflets (downloadable PDFs).

For your convenience, the Ph. Eur. RS catalogue is published daily and can be downloaded in in PDF format and in XML format.

When stocks of a given reference standard are low, the EDQM reserves the right to limit the quantities sold to each user to ensure that as many users as possible will receive at least some of the quantities available. Restrictions on quantities are applied at the time the purchase order is received.

Following a request from many users, the quantities allowed in case of sales restrictions now appear in the online catalogue as well as in the catalogue in XML format.

The EDQM is also responsible for the establishment, preparation, storage and distribution of WHO International Chemical Reference Standards (ICRS) and International Standards for Antibiotics (ISA).

How to place an RS order

If you wish to place an order, you can send your request to the EDQM either:

• via the WebStore;
• or by to [ protected] (in this case, please ensure that your order, on your company letterhead, states both the catalogue code and substance name and is attached to your ).

A video has been prepared to help user ordering through the RS WebStore.

The EDQM helps the users to test some draft texts proposed in Pharmeuropa through Qualified Samples

In some cases, ‘qualified samples’ are made available by the EDQM at the time of publication in Pharmeuropa to allow users to check the changes (e.g. to the related substances test) proposed during the public enquiry and best prepare for the implementation of the monograph.

Where a qualified sample is available, it is described in the briefing note of the Pharmeuropa monograph and may be ordered free of charge by raising a request in the EDQM HelpDesk. After use, users are kindly requested to share their results with the EDQM.

To place an order via the EDQM HelpDesk, please click on European Pharmacopoeia and choose the category Question about General Chapters and Monographs. Providing us with your full shipping address and the title of the corresponding Ph. Eur. monograph, while stating ‘Qualified sample’ in the subject of the query, will help us to rapidly process your request.

For more Praziquantel Api Production Plantinformation, please contact us. We will provide professional answers.

Higher-order multicomponent crystals as a strategy to decrease the IC50 parameter: the case of praziquantel, niclosamide and acetic acid

Under a Creative Commons license Open access

Highlights

• •Cocrystal solvate has higher in vitro activity than pristine drugs and binary solids.
• •Five mechanochemical routes from individual coformers or preformed binary solids.
• •The new solid, confirmed by SS-NMR, crystallizes in P-1 and was solved via PXRD-DFT.

Abstract

We successfully assembled via mechanochemistry 3 anthelmintic molecules in a single stable solid, namely praziquantel (PZQ), niclosamide (NCM), and acetic acid (AA). We obtained a cocrystal solvate with largely superior anthelmintic activity against in vitro Schistosoma mansoni adults and, notably, against Newly Transformed Schistosomula compared to pure individual drugs (i.e., PZQ and NCM) and to its binary counterparts (i.e., PZQ-NCM cocrystal and PZQ-AA monosolvate).We also demonstrated 5 different strategies for synthesizing the ternary cocrystal not only starting from individual coformers but also by combining different building blocks (i.e. preformed binary solids). The new phase was only obtainable through mechanochemistry as comparative slurry experiments were unsuccessful. Even though the ternary solid was crystallized through all five investigated routes, a pure phase was obtained by milling the preformed praziquantel-acetic acid monosolvate and raw niclosamide in an equimolar ratio for 60 min in the presence of 160 μL of acetic acid. Acetic acid acted both as a solvate-forming molecule and a liquid additive.The purity of this new solid phase was confirmed by SS-NMR spectrum, also suggesting the presence of one independent molecule of PZQ, one of NCM and one of AA, as confirmed by 1H NMR. The cocrystal structure was solved from the Synchrotron powder X-ray pattern and optimized via DFT calculations. Crystallizing in the triclinic P-1 space group, the solid comprises one PZQ, one NCM, and one AA molecule linked via hydrogen bonds, as demonstrated by FT-IR analyses. The solid phase exhibits small plate agglomerates, as observed through SEM analysis, a desolvation event at ∼107 °C (TGA weight loss: 9.77 %), and physical stability over 24 months at room temperature.The drastic reduction in IC50 (0.01 μM against Newly Transformed Schistosomula and Schistosoma mansoni adults) of the new solid fully justifies the ambitious challenge of incorporating more than two components into a single crystalline phase, underscoring the pivotal role of the ternary system in enhancing bioactivity. This finding highlights the need to tackle the next challenge: identifying the most suitable oral dosage form for a cocrystal solvate, a requirement that remains unmet in the pilot studies conducted in this work.

Graphical abstract

Keywords

Praziquantel-niclosamide-acetic acid cocrystal solvatePharmaceutically acceptable cocrystal solvateSynchrotron X-ray powder diffractionBuilding-blocks approachIn vitro anthelmintic activityIn vivo preliminary tests

Abbreviations

APIsactive pharmaceutical ingredientsPZQpraziquantelNCMniclosamideAAacetic acidDSCdifferential scanning calorimetryPXRDPowder X-ray diffractionLAGliquid-assisted grindingNGneat grindingFT-IRinfrared spectroscopySSNMRsolid-state NMRDFTDensity Functional TheorySEMscanning electron microscopyCSDCambridge Structural DatabaseNTSNewly Transformed SchistosomulaS. mansoniadult Schistosoma mansoniWBRworm burden reductionTMStetramethyl silaneASUasymmetric unitRHrelative humidity

Data availability

CCDC number contains the crystallographic data for the cocrystal solvate, obtainable for free from The Cambridge Crystallographic Data Centre via https://www.ccdc.cam.ac.uk/structures.

Cited by (0)

© The Authors. Published by Elsevier B.V.