FARMACOPEEA

ROMN
EDIIA A X-A

SUPLIMENT 2004

COMISIA DE COORDONARE A
FARMACOPEEI ROMNE

PREEDINTE:

Farm.pr. Magdalena Bdulescu - Preedinte ANM

SECRETAR:

Farm.pr. Daniela Enache - ef Departament integrare

european, farmacopee, juridic, legislaie, ANM

MEMBRI

Dr.farm.pr. Felicia Gtlan - Director Direcia General

Farmaceutic, Ministerul Sntii (pn n decembrie 2003)

Farm.pr.

Otilia

Ulieru

Director

Direcia

General

Farmaceutic, Ministerul Sntii (din decembrie 2003)

Prof.dr. Dumitru Lupuleasa Decan al Facultii de

Farmacie din Bucureti

Prof.dr. Robert Sndulescu - Decan al Facultii de

Farmacie din Cluj - Napoca

Prof.dr. Ursula Stnescu - Decan al Facultii de Farmacie

din Iai

Prof.dr. Maria Titica-Dogaru - Decan al Facultii de

Farmacie din Tg.Mure

Farm.pr. Rodica Bdescu Vicepreedinte ANM

Farm.pr. Nela Vlceanu ef Departament evaluare autorizare ANM

Farm.pr. Liliana Cotenescu ef Departament control

materii prime i produse finite ANM

Biolog pr. Anca Moraru ef Departament control produse

biologice ANM

Dr.farm.pr. Simona Raicu ef Departament inspecie

farmaceutic ANM

Farm.pr. Victoria Subiric

Departament evaluare -

autorizare ANM

Farm.sp. Andreea Varvara

- Departament control materii

prime i produse finite ANM

Experi forme farmaceutice i metode farmacotehnice

Prof. dr. Sorin Leucua - Facultatea de Farmacie din Cluj

Prof. dr. Ana Maria Dumitrescu - Facultatea de Farmacie

din Bucureti

Prof. dr. Eliza Gafieanu - Facultatea de Farmacie din Iai

Conf. dr.Victoria Hrju - Fac. de Farmacie din Bucureti

ef lucrri Adriana Ciurba - Fac. de Farmacie din Tg.Mure

ef lucrri Marcela Achim - Facultatea de Farmacie din Cluj

COLECTIV DE REDACTARE

Farm.pr. Daniela Enache - Redactor de carte

Ing. chim. Liliana Stroie

Farm.pr. Maria-Gabriela Suliman

Supliment 2004

PREFA
Romnia a aderat la Convenia privind elaborarea Farmacopeei
Europene, din cadrul Consiliului Europei i a devenit membru cu
drepturi depline ncepnd din 24.09.2003.
Parlamentul Romniei a adoptat legile pentru aderarea Romniei
la Convenie i la Protocolul la Convenia privind elaborarea
Farmacopeei Europene (Legile nr.148 din 03.04.2001 i nr.98 din
05.04.2002), care au fost promulgate prin Decretul nr. 159/2002
de Preedintele Romniei i publicate n Monitorul Oficial al
Romniei.
Convenia privind elaborarea Farmacopeei Europene a fost
adoptat la Strasbourg n 1964 i este format la ora actual din
32 de pri semnatare: Anglia, Austria, Belgia, Bosnia i
Heregovina, Republica Ceh, Cipru, Croaia, Danemarca, Elveia,
Estonia, Finlanda, Frana, Germania, Grecia, Irlanda, Islanda,
Italia, Letonia, Luxemburg, Macedonia, Norvegia, Olanda,
Portugalia, Romnia, Serbia i Muntenegru, Slovenia, Slovacia,
Spania, Suedia, Turcia, Ungaria, i Uniunea European.
Comisia Farmacopeei Europene este format din delegaiile
naionale ale prilor semnatare ale Conveniei.
Prin aderarea Romniei la Convenie standardele de calitate
ale Farmacopeei Europene vor deveni obligatorii pentru toate
medicamentele de uz uman i veterinar fabricate n Romnia,
ct i pentru cele din import.
Agenia Naional a Medicamentului a adoptat treptat o serie de
monografii i metode generale de analiz din Farmacopeea
European, care au devenit norme obligatorii n domeniul calitii
medicamentului din Romnia i care au fost publicate n
Suplimentele Farmacopeei Romne ediia a X-a.
Suplimentul 2004 al Farmacopeei Romne ediia a X-a este
redactat i publicat de Agenia Naional a Medicamentului, creia
i revine elaborarea Farmacopeei Romne i a Suplimentelor

Farmacopeea Romn ediia a X-a

acesteia, n temeiul prevederilor articolului 4 litera i) din Ordonana

Guvernului Nr. 125 / 29.08.1998 privind nfiinarea, organizarea i
funcionarea Ageniei Naionale a Medicamentului, aprobat cu
modificri i completri prin Legea nr. 594/2002, cu modificrile i
completrile ulterioare.
Suplimentul 2004 al Farmacopeei Romne ediia a X-a cuprinde
capitole generale, monografii individuale i generale, traduse i
armonizate din Farmacopeea European ediia a 4-a i
Addendumurile 4.1; 4.2; 4.3; 4.4; 4.5; 4.6 i 4.7, precum i
reactivii necesari determinrilor prevzute n respectivele texte.
Avnd n vedere c textele cuprinse n Suplimentul 2004 al
Farmacopeei Romne ediia a X-a sunt traduse i armonizate din
Farmacopeea European, n caz de litigiu se iau ca referin
textele din versiunile oficiale publicate de Consiliul Europei (n
limbile englez i francez).
Trebuie menionat, de asemenea, c este posibil s intervin
anumite modificri n ediiile i Addendumurile ulterioare ale
Farmacopeei Europene, cu referire la textele traduse i cuprinse
n Suplimentul 2004 al Farmacopeei Romne ediia a X-a.
Suplimentul 2004 al Farmacopeei Romne ediia a-X-a va intra n
vigoare dup ce va fi publicat de ctre Agenia Naional a
Medicamentului i va abroga orice alte prevederi contrare din
Farmacopeea Romn ediia a-X-a i Suplimentele acesteia.

Farm. pr. Magdalena Bdulescu

Preedintele Ageniei Naionale a Medicamentului

Supliment 2004

PREFACE
Romania acceded to the Convention on the elaboration of the
European Pharmacopoeia, of the European Council and became
a full member starting with 24.09.2003.
The Romanian Parliament has adopted the Laws regarding
Romanias accession to the Convention on the elaboration of the
European Pharmacopoeia (Laws No. 148 from 03.04.2001 and
No. 98 from 05.04.2002), that were promulgated through the
Decree No. 159/2002 by the President of Romania and published
in the Romanian Official Monitor.
The Convention on the elaboration of the European
Pharmacopoeia was adopted in Strasbourg in 1964 and it is
signed in the present by 32 parties: Austria, Belgium, BosniaHerzegovina, Czech Republic, Cyprus, Croatia, Denmark, Estonia,
Finland, France, Germany, Greece, Hungary, Ireland, Iceland,
Italy, Latvia, Luxembourg, Macedonia, Norway, Netherlands,
Portugal, Romania, Serbia and Montenegro Slovenia, Slovakia,
Spain, Sweden, Switzerland, Turkey, United Kingdom and the
European Union.
By Romanias accession to the Convention, the quality
standards of the European Pharmacopoeia will become
mandatory for all the medicinal products for human and
veterinary use manufactured in Romania, as well as for all the
imported ones.
The National Medicines Agency has gradually adopted a series of
monographs and general analysis methods from the European
Pharmacopoeia, that have become mandatory standards in the
medicines quality domain within Romania and that have been
published in the Supplements of the Romanian Pharmacopoeia,
the Xth edition.
The Supplement 2004 of the Romanian Pharmacopoeia, the Xth
edition, has been drawn up and published by the National

Farmacopeea Romn ediia a X-a

Medicines Agency, who also takes care of the drawing up of the

Romanian Pharmacopoeia and its Supplements, based on the
Article 4 paragraph i) from the Governments Ordinance No. 125 /
29.08.1998 regarding the setting up, the organisation and the
functioning of the National Medicines Agency, approved with
changes and completions through Law No. 594/2002, with its
further changes and completions.
The Supplement 2004 of the Romanian Pharmacopoeia, the X th
edition, contains general chapters, general and individual
monographs, translated and harmonised from the European
Pharmacopoeia, the 4th edition and the 4.1; 4.2; 4.3; 4.4; 4.5;
4.6 and 4.7 Addendums, as well as the reagents necessary in the
determinations provided in the respective texts.
Regarding that all the texts, gathered in the Supplement 2004 of
the Romanian Pharmacopoeia, the Xth edition, are translated and
harmonised from the European Pharmacopoeia; in case of
litigations, the texts from the official versions published by the
European Council (in English and French) will be referred to.
It has to be mentioned, also, that it may be possible for some
modifications to occur in the subsequent editions and Addendums
of the European Pharmacopoeia, with reference to the translated
texts comprised in Supplement 2004 of the Romanian
Pharmacopoeia, the Xth edition.
The provisions of the Supplement 2004 of the Romanian
Pharmacopoeia, the Xth edition, will come in force after its previous
publishing by the National Medicines Agency.

Senior Pharm. Magdalena Bdulescu

President of the National Medicines Agency

Supliment 2004

CUPRINS
Prefa - Suplimentul 2004 al Farmacopeei Romne ediia a X-a

PREVEDERI GENERALE
1.1.
Generaliti.21
1.2. Alte dispoziii aplicabile monografiilor i capitolelor
generale.24
1.3. Capitole generale...27
1.4. Monografii28
1.5. Abrevieri i simboluri.36
1.6. Sistemul internaional de uniti (SI) utilizat de
Farmacopeea European i corespondena cu alte
Uniti..40
MONOGRAFII DE FORME FARMACEUTICE
Glosar (01/2002 : 1502)..49
Capsule (01/2002 : 0016)...52
Comprimate (04/2002 : 0478)59
Creioane (01/2002 : 1154)..69
Granule (04/2003 : 0499)71
Gume medicamentoase masticabile (01/2002 : 1239)..76

Farmacopeea Romn ediia a X-a

Preparate

auriculare

(01/2002

0652)

..78
Preparate bucofaringiene (04/2002 : 1807).83
Preparate de inhalat (04/2003 : 0671)..94
Preparate farmaceutice presurizate (01/2002 : 0523).108
Preparate lichide pentru aplicaii cutanate (04/2003 : 0927)..110
Preparate lichide pentru uz oral (04/2003 : 0672)113
Preparate nazale (01/2002 : 0676).120
Preparate oftalmice (04/2003 : 1163).127
Preparate parenterale (01/2002 : 0520).135
Preparate pentru irigaii (01/2002 : 1116)..143
Preparate rectale (01/2002 : 1145).145
Preparate semisolide pentru aplicaii cutanate
(01/2002 : 0132).152
Preparate vaginale (01/2002 : 1164)..159
Pulberi orale (04/2003 : 1165).166
Pulberi pentru aplicaii cutanate (01/2002 : 1166)168
Sisteme terapeutice transdermice (01/2002 : 1011)171
Spume medicamentoase (01/2002 : 1105)...174
Tampoane medicamentoase (01/2002 : 1155).178
TEXTE REVIZUITE :
1. Din Farmacopeea European ediia a 4-a
2.9.5. Uniformitatea masei preparatelor unidoz181
2.9.6. Uniformitatea coninutului preparatelor unidoz...183

Supliment 2004

10

2.9.17. Determinarea volumului extractibil pentru preparate

parenterale.185
3.1.10. Materiale pe baz de poli(clorur de vinil) neplastifiat,
pentru condiionarea soluiilor apoase neinjectabile...187
3.1.11. Materiale pe baz de poli(clorur de vinil) neplastifiat,
pentru condiionarea formelor solide cu administrare pe
cale oral195
Ap purificat (07/2002 : 0008)...203
Ap pentru preparate injectabile (07/2002 : 0169)...208
2. Din Farmacopeea Romn ediia a X-a
Hotrrea Consiliului tiinific al Ageniei Naionale a
Medicamentului nr. 7/17.01.2003, referitoare la modificarea
ncadrrii unor preparate farmaceutice n categoria Separanda
sau Venena, din Farmacopeea Romn, ediia a X-a 215
Anexa nr.I216
Anexa nr.II - tabel Separanda..218
Anexa nr. III tabel Venena.221
Ordin al ministrului sntii i familiei nr. 95/06.02.2003, pentru
aprobarea hotrrii Consiliului tiinific al Ageniei Naionale a
Medicamentului nr. 7/17.01.2003, referitoare la modificarea
ncadrrii unor preparate farmaceutice n categoria Separanda
sau Venena, din Farmacopeea Romn, ediia a X-a .222

TEXTE SUPRIMATE
1. Din Farmacopeea European ediia a 4-a
2.9.21. Contaminarea cu particule: metode microscopice

11

Farmacopeea Romn ediia a X-a

TERMENI STANDARD ROMNETI

Hotrrea Consiliului tiinific al Ageniei Naionale a
Medicamentului nr. 4/27.06.2003, referitoare la aprobarea
Termenilor standard utilizai n Romnia pentru formele
farmaceutice, cile de administrare i ambalajele primare, n
concordan cu cei adoptai de Farmacopeea European ediia a
4-a i Consiliul Europei..225
Anexa - Termeni Standard Romneti226
Introducere i ghid de utilizare.228
1. Forme farmaceutice..231
Preparate orale - forme lichide i semisolide
Preparate orale - forme solide
Preparate bucofaringiene
Preparate dentare
Preparate cutanate i transdermice
Preparate oftalmice
Preparate auriculare
Preparate nazale
Preparate vaginale
Preparate rectale
Preparate de inhalat
Preparate parenterale
Implanturi
Preparate pentru dializ
Preparate intravezicale i uretrale
Preparate traheopulmonare

Supliment 2004

12

Preparate endocervicale
Preparate intrauterine
Varia
2. Cile de administrare259
3. Ambalaje primare, sisteme de nchidere i de
administrare264
INDEX DE REACTIVI271

REACTIVI
(Necesari determinrilor prevzute n monografiile acestui Supliment )

4.1.1. Reactivi.280
4.1.2. Soluii etalon pentru controlul limitelor de impuriti.303
4.1.3. Soluii tampon..305
4.2.2. Soluii titrate.306
INDEX ALFABETIC...311

13

Farmacopeea Romn ediia a X-a

CONTENTS
Preface - Supplement 2004 of the Romanian Pharmacopoeia X th
edition

GENERAL NOTICES
1.1. General statements..21
1.2. Other provisions applying to general chapters and
monographs.24
1.3. General chapters..27
1.4. Monographs..28
1.5. Abbreviations and symbols.36
1.6. Units of the international system (SI) used in the
pharmacopoeia and equivalence with other units...40

MONOGRAPHS ON DOSAGE FORMS

Glossary (01/2002 : 1502)..49
Capsules (01/2002 : 0016).52
Chewing gums, medicated (01/2002 : 1239)..76
Ear preparations (01/2002 : 0652)78
Eye preparations (04/2003 : 1163).127
Foams, medicated (01/2002 : 1105)...174
Granules

(04/2003

..71

0499)

Supliment 2004

14

Liquid preparations for cutaneous application

(04/2003 : 0927).110
Liquid preparations for oral use (04/2003 : 0672)113
Oromucosal preparations (04/2002 : 1807).83
Parenteral preparations (01/2002 : 0520)..135
Patches, transdermal (01/2002 : 1011)..171
Preparations for inhalation (04/2003 : 0671)...94
Preparations for irrigation (01/2002 : 1116)..143
Pressurised pharmaceutical preparations (01/2002 : 0523)...108
Powders for cutaneous application (01/2002 : 1166)..168
Powders, oral (04/2003 : 1165)...166
Rectal preparations (01/2002 : 1145).145
Nasal preparations (01/2002 : 0676)..120
Semi-solid preparations for cutaneous application
(01/2002 : 0132).152
Sticks (01/2002 : 1154)...69
Tablets (04/2002 : 0478).59
Tampons medicated (01/2002 : 1155)178
Vaginal preparations (01/2002 : 1164)...159

REVISED TEXTS
1. Of the European Pharmacopoeia 4th edition
2.9.5. Uniformity of mass of single-dose preparations181
2.9.6. Uniformity of content of single-dose preparations.183
2.9.17. Test for extractable volume of parenteral

15

Farmacopeea Romn ediia a X-a

preparations..185
3.1.10. Materials based on non-plasticised poly(vinylchloride)
for containers for non-injectable, aqueous solutions..187
3.1.11. Materials based on non-plasticised poly(vinylchloride)
for

containers

for

dry

dosage

forms

for

oral

administration..195
Water for injections (07/2002 : 0169).208
Water, purified (07/2002 : 0008)..203
2. Of the Romanian Pharmacopoeia Xth edition
Decision of the National Medicines Agency Scientific Council
No. 7 from the17th of January 2003, regarding the change of the
framing of certain pharmaceutical preparations from Separanda
or Venena category, from the Romanian Pharmacopoeia, Xth
edition.215
Annex no. I..216
Annex no. II Table Separanda..218
Annex no. III Table Venena .221
Order of the Minister of Health and Family No.95 from the 6 th of
February 2003, for approval of the National Medicines Agency
Scientific Council, No. 7 from the17th of January
2003,
regarding the change of the framing of certain pharmaceutical
preparations from Separanda or Venena category, from the
Romanian Pharmacopoeia, Xth edition 222

DELETED TEXTS
1. Of the European Pharmacopoeia 4th edition
2.9.21. Particulate contamination : microscope method

Supliment 2004

16

ROMANIAN STANDARD TERMS

Decision of the National Medicines Agency Scientific Council No.
4 from the 27th of June 2003, regarding the approval Standard
Terms used in Romania for pharmaceutical dosage forms, routes
of administration and containers, in accordance with those from
the European Pharmacopoeia, 4th edition and European Council
225
Annex Romanian Standard Terms 226
Introduction and Guidance for use ...228
1. Pharmaceutical dosage forms ...231
Oral preparations - liquid and semi-solid forms
Oral preparations - solid forms
Oromucosal preparations
Preparations for dental use
Cutaneous and transdermal preparations
Eye preparations
Ear preparations
Nasal preparations
Vaginal preparations
Rectal preparations
Preparations for inhalation
Parenteral preparations
Implants
Preparations for dialysis
Preparations for intravesical and urethral use
Tracheopulmonary preparations
Endocervical preparations

17

Farmacopeea Romn ediia a X-a

Intrauterine preparations
Miscellaneous
2. Routes of administration 259
3. Containers..264

REAGENTS INDEX..271
REAGENTS
(Use for requirement tests in this Supplement monographs)

4.1.1. Reagents..280
4.1.2. Standard solutions for limit tests..303
4.1.3. Buffer solutions305
4.2.2. Volumetric solutions ..306

ALPHABETICAL INDEX.311