Croscarmellose Sodium

Croscarmellose Sodium 1 Nonproprietary Names

BP: Croscarmellose sodium PhEur: Carmellosum natricum conexum USPNF: Croscarmellose sodium 2 Synonyms  Ac-Di-Sol; crosslinked carboxymethylcellulose sodium; Explocel; modified cellulose gum; Nymcel ZSX; Pharmacel XL; Primellose; Solutab; Vivasol. 3 Chemical Name and CAS Registry Number Cellulose,

carboxymethyl ether, sodium salt, crosslinked [74811-65-7] 4 Empirical Formula and Molecular Weight

Croscarmellose sodium is a crosslinked polymer of carboxymethylcellul ose sodium. See Carboxymethylcellulose sodium. 5 Structural Formula See Carboxymethylcellulose sodium. 6 Functional Category

Tablet and capsule disintegrant. 7 Applications in Pharmaceutical Formulation or Technology (3–13) Croscarmellose sodium is used in oral pharmaceutical formulations as a disintegrant for capsules, (1,2) tablets,(3–

and granules. In tablet formulations, croscarmellose sodium may be used in both direct-compression and wetgranulation processes. When used in wet granulations, the croscarmellose sodium should be added in both the wet and dry stages of the process (intra- and extragranularly) so that the wicking and swelling ability of the disintegrant is best utilized.(11,12) Croscarmellose sodium at concentrations up to 5% w/w may be used as a tablet disintegrant, although normally 2% w/w is used in tablets prepared by direct compression and 3% w/w in tablets prepared by a wet-granulation process.

8 Description

Croscarmellose sodium occurs as an odorless, white or grayishwhite powder.

9 Pharmacopeial Specifications See Table II. Table II: Pharmacopeial specifications specifications for croscarmellose croscarmellose sodium.

10 Typical Properties

5.0–7.0 in aqueous dispersions.  Acidity/alkalinity: pH = 5.0– Bonding index: 0.0456 Brittle fracture index: 0.1000 Density (bulk): 0.529 g/cm3 for Ac-Di-Sol(7) Density (tapped): 0.819 g/cm3 for Ac-Di-Sol(7) Density (true): 1.543 g/cm3 for Ac-Di-Sol(7) Particle size distribution:  Ac-Di-Sol: not more than 2% retained on a #200 (73.7 mm)

mesh and not more than 10% retained on a #325 (44.5 mm) mesh. Pharmacel XL: more than 90% less than 45 mm, and more

than 98% less than 100 mm in size. Solubility: insoluble in water, although croscarmellose sodium rapidly swells to 4– 4–8 times its original volume on

contact with water. Practically insoluble in acetone, ethanol and toluene. Specific surface area: 0.81– 0.81–0.83m2 /g 11 Stability and Storage Conditions

Croscarmellose sodium is a stable though hygroscopic material. A model tablet formulation prepared by direct compression, with croscarmellose sodium as a disintegrant, showed no significant difference in drug dissolution after storage at 308C for 14 months. (9) Croscarmellose sodium should be stored in a well-closed container in a cool, dry place. 12 Incompatibilities

The efficacy of disintegrants, such as croscarmellose sodium, may be slightly reduced in tablet formulations prepared by either the wet-granulation or direct-compression process that contain hygroscopic excipients such as sorbitol.(10) Croscarmellose sodium is not compatible with strong acids or with soluble salts of iron i ron and some other metals such as aluminum, mercury, and zinc. 13 Method of Manufacture

Alkali cellulose is prepared by steeping cellulose, obtained from wood pulp or cotton fibers, in sodium hydroxide solution. The alkali cellulose is then reacted with sodium monochloroacetate to obtain carboxymethylcellulose sodium. After the substitution reaction is completed and all of the sodium hydroxide has been used, the excess sodium monochloroacetate slowly hydrolyzes to glycolic acid. The glycolic acid changes a fe w of the of the sodium carboxymethyl groups to the free acid and catalyzes the formation of crosslinks to produce croscarmellose sodium. The croscarmellose sodium is then extracted with aqu eous alcohol and any remaining sodium chloride or sodium glycolate is removed. After purification, croscarmellose sodium of purity greater than 99.5% is obtained. (4) The croscarmellose sodium may be milled to break the polymer fibers into shorter lengths and hence improve its flow properties. 14 Safety

Croscarmellose sodium is mainly used as a disintegrant in oral pharmaceutical formulations and is generally regarded as an essentially nontoxic and nonirritant material. However, oral consumption of large amounts of croscarmellose sodium may have a laxative effect, although the quantities used in solid dosage formulations are unlikely to cause such problems. In the UK, croscarmellose sodium is accepted for use in dietary supplements. The WHO has not specified an acceptable daily i ntake for the related substance carboxymethylcellulose sodium, used as a food additive, since the levels necessary to achieve a desired effect were not considered sufficient to be a hazard to health. (14) See also Carboxymethylcellulose sodium.

15 Handling Precautions

Observe normal precautions appropriate to the circumstances and quantity of material handled. Croscarmellose sodium may be irritant to the eyes; eye protection is recommended. 16 Regulatory Status

Included in the FDA Inactive Ingredients Guide (oral capsules, granules, sublingual tablets, and tablets). Included in nonparenteral medicines licensed in the UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients. 17 Related Substances

Carboxymethylcellulose calcium; carboxymethylcellulose sodium. 18 Comments

Typically, the degree of substitution (DS) for croscarmellose sodium is 0.7. Hand book of pharmaceutical

1 Nama Nonproprietary BP: Croscarmellose sodium PhEur: Carmellosum natricum conexum USPNF: Croscarmellose sodium

2 Sinonim Ac-Di-Sol; natrium karboksimetilselulosa silang; Explocel; ganggang selulosa termodifikasi; Nymcel ZSX; Pharmacel XL; Primellose; Solutab; Vivasol.

3 Nama Kimia dan Nomor Pendaftaran CAS Selulosa, karboksimetil eter, garam natrium, ikatan silang [74811-65-7]

4 Rumus Empiris dan Berat Molekul Natrium kroskarmelosa adalah polimer silang dari natrium karboksimetilselulosa. Lihat Carboxymethylcellulose sodium. 5 Formula Struktural Lihat Carboxymethylcellulose sodium.

6 Kategori Fungsional Tablet dan disintegran kapsul. 7 Aplikasi dalam Formulasi Farmasi atau Teknologi Natrium kroskarmelosa digunakan dalam formulasi farmasi oral sebagai disintegran untuk kapsul, (1,2) tablet, (313) dan granul. Dalam formulasi tablet, natrium kroskarmelosa dapat digunakan baik dalam p roses kompresi langsung dan granulasi basah. Ketika digunakan dalam granulasi basah, natrium kroskarmelosa harus ditambahkan baik pada tahap basah dan kering dari proses (intra dan ekstragranular) sehingga kemampuan wicking dan pembengkakan disintegran paling baik digunakan. (11,12) Croscarmellose sodium di konsentrasi

hingga 5% b / b dapat digunakan sebagai disintegran tablet, meskipun biasanya 2% b / b digunakan dalam tablet yang dibuat dengan kompresi langsung dan 3% b / b dalam tablet yang disiapkan dengan proses granulasi basah. 8 Keterangan Natrium kroskarmelosa muncul sebagai bubuk putih yang tidak berbau, putih atau keabu-abuan.

10 Properti Khas Keasaman / alkalinitas: pH = 5,0-7,0 dalam dispersi berair. Indeks pengikat: 0,0456 Indeks fraktur rapuh: 0,1000 Densitas (curah): 0,529 g / cm3 untuk Ac-Di-Sol (7) Kepadatan (disadap): 0,819 g / cm3 untuk Ac-Di-Sol (7) Kepadatan (true): 1,543 g / cm3 untuk Ac-Di-Sol (7) Distribusi ukuran partikel: Ac-Di-Sol: tidak lebih dari 2% disimpan pada # 200 (73,7 mm) mesh dan tidak lebih dari 10% disimpan pada mesh # 325 (44,5 mm). Pharmacel XL: lebih dari 90% kurang dari 45 mm, dan banyak lagi dari 98% kurang dari 100 mm. Kelarutan: tidak larut dalam air, meskipun natrium kroskarmelosa cepat membengkak menjadi 4-8 kali volume aslinya saat bersentuhan dengan air. Praktis tidak larut dalam aseton, etanol dan toluena. Luas permukaan spesifik: 0,81-0,83m2 / g

11 Kondisi Stabilitas dan Penyimpanan Natrium kroskarmelosa adalah bahan higroskopis yang stabil. Formulasi tablet model yang disiapkan dengan kompresi langsung, dengan natrium kroskarmelosa sebagai disintegran, tidak menunjukkan

perbedaan yang signifikan dalam pembubaran obat setelah penyimpanan pada 308C selama 14 bulan. (9) Natrium kroskarmelosa harus disimpan dalam keadaan tertutup wadah di tempat yang sejuk dan kering. 12 Inkompatibilitas Kemanjuran disintegrants, seperti natrium kroskarmelosa, dapat sedikit direduksi dalam formulasi tablet yang dibuat dengan proses granulasi basah atau proses kompresi langsung yang mengandung eksipien higroskopis seperti sorbitol. (10) Natrium kroskarmelosa tidak kompatibel dengan asam kuat atau dengan garam larut besi dan beberapa logam lain seperti aluminium, merkuri, dan seng. 13 Metode Pembuatan Selulosa alkali dibuat dengan mendidih selulosa, diperoleh dari pulp kayu atau serat kapas, dalam larutan natrium hidroksida. Selulosa alkali kemudian direaksikan dengan natrium monokloroasetat untuk memperoleh natrium karboksimetilselulosa. Setelah reaksi substitusi selesai dan semua natrium hidroksida telah digunakan, natrium monokloroasetat yang berlebih secara perlahan menghidrolisis menjadi asam glikolat. Asam glikolat mengubah beberapa gugus natrium karboksimetil menjadi asam bebas dan mengkatalisis pembentukan ikatan silang untuk menghasilkan natrium kroskarmelosa. Natrium kroskarmelosa kemudian diekstraksi dengan alkohol berair dan natrium klorida atau natrium glikolat yang tersisa dihilangkan. Setelah pemurnian, natrium silang-silang kemurnian lebih besar dari 99,5% diperoleh. (4) Natrium k roskarmelosa dapat digiling untuk memecahkan serat polimer menjadi panjang yang lebih pendek dan karenanya meningkatkan sifat alirannya.

14 Keselamatan Natrium kroskarmelosa terutama digunakan sebagai disintegrant dalam formulasi farmasi oral dan umumnya dianggap sebagai bahan yang pada dasarnya tidak beracun dan tidak berbahaya. Namun, konsumsi oral sejumlah besar natrium kroskarmelosa mungkin memiliki efek pencahar, meskipun jumlah yang digunakan dalam formulasi dosis padat tidak mungkin menyebabkan masalah seperti itu. Di Inggris, natrium kroskarmelosa diterima untuk digunakan dalam suplemen diet. WHO belum menetapkan asupan harian yang dapat diterima untuk substansi yang terkait karboksimetilselulosa natrium, digunakan sebagai aditif makanan, karena tingkat yang diperlukan untuk mencapai efek yang diinginkan tidak dianggap cukup untuk menjadi bahaya bagi kesehatan. (14) Lihat juga Carboxymethylcellulose sodium.

15 Tindakan Pencegahan Penanganan

Amati kewaspadaan normal sesuai dengan keadaan dan kuantitas material yang ditangani. Natrium kroskarmelosa dapat mengiritasi mata; pelindung mata dianjurkan.

16 Status Regulasi Termasuk dalam FDA Inactive Ingredients Guide (kapsul oral, granula, tablet sublingual, dan tablet). Termasuk dalam obat-obatan nonparenteral yang berlisensi di Inggris. Termasuk dalam Daftar Kanada Bahan Non-obat yang Dapat Diterima.

17 Zat Terkait Karboksimetilselulosa kalsium; carboxymethylcellulose sodium.

18 Komentar Biasanya, tingkat substitusi (DS) untuk natrium kroskarmelosa adalah 0,7.

martindale 36

Croscarmellose Sodium (USAN) Carmellosum natricum conexum; Croscarmellose sodique; Croscarmelosa sódica; Crosslinked Carboxymethylcellulose Sodium; E468; Kroskarmelioze ˙s natrio druska; Kroskarmelloosi Kroskarmello osi natrium; Kroskarmello Kroskarmellosnatrium; snatrium; Kroskarmelosa sodná s ůl; Kroskarmeloz Kroskarmeloza a sodowa; Kroszkarmellóz-nátrium; Modified Cellulose Gum. Pharmacopoeias. In Eur. (see p.vii) and Jpn. Also in USNF . Ph. Eur. 6.2 (Croscarmellose Sodium) . A cross-linked polymer of carmellose sodium. A white or greyish-white powder. Practically Practically insoluble in dehydrated alcohol, in acetone, and in toluene. A 1% suspension in water has a pH of 5.0 to 7.0. USNF 26 (Croscarmellose Sodium) . The sodium salt of a crosslinked partly O(carboxymethylated) (carboxym ethylated) cellulose. A white, freeflowing powder. Partially soluble in water; insoluble in alcohol, in ether, and in other organic solvents. pH of a dispersion containing 1 g mixed with 100 mL of water for 5 minutes is between 5.0 and 7.0. Uses and Administration Carmellose calcium and carmellose sodium have a variety of pharmaceutical uses, including use as suspending, thickening, and emulsifying agents, and as disintegrants, binders, and coating agents in tablets. Carmellose sodium is also used as an emulsifier or st abiliser in the food industry. Croscarmellose Croscarme llose sodium is used as a tablet disintegrant. Carmellose sodium is used topically as an ingredient of protective preparations for stoma care, in the management of wounds, and for the mechanicall protection of oral and perioral lesions, such as mouth ulceration (p.1700). It is also used, mechanica in concentrations of up to 1%, in artificial saliva preparations for the treatment of dry mouth (p.2140), and in eye drops for the management management of dry eye (p.2140). Carmellose sodium given orally absorbs water and acts as a bulkforming agent; t he volume of faeces is increased and peristalsis promoted. It is used in the treatmen treatmentt of constipation (p.1693). Carmellose sodium has been included in preparations to control appetite in the management management of obesity (p.2149) but there is little evidence of efficacy. For  precautions to be observed with with bulkforming agents, see see under Methylcellulose, Methylcellulose, p.2145. p.2145. Preparations B P 2008: 2008: Carmellose Sodium Eye Drops; Carboxymethylcellulo ylcellulose se Sodium Paste; Carboxymeth Carboxymethylcellulose ylcellulose Sodium Tablets. USP 31 31:: Carboxymeth Proprietary Preparations (details are given in Part 3) Lagrima†; Aqua Lent Lent Lubricante; Aquacel; Aquacel; Aucic; Cellufresh†; Cellufresh†; Celluvisc†;  A r g .:  Aqua Lent Lagrima†; Comfeel; Comfeel Plus Transparente; Natura Fresh; Nu- Derm Hidrocoloide; Refresh Liquigel; Refresh Tears; A us tral.:  Aquacel†;  Aquacel†; Cellufresh;  Cellufresh; Celluvisc; Refresh Liquigel; Refresh Tears Plus†; A us tri a: Celluvisc; Cellufresh;; Ecofilm; Fresh Tears; Lacrifilm; Salivan; Belg.: Gelilact; Braz.: Cellufresh  Aquacel†;; Refresh Celluvisc; Celluvisc; Refresh Liquigel; Liquigel; Refresh Plus; Plus; Ref resh resh Canad.:  Aquacel† Tears; Chile: Refresh Liquigel; Refresh Tears; Cz.: Cellufluid; Denm.: Celluvisc; Askina Biofilm†; Biatain; Biatain; Celluvisc; Celluvisc; Clip Fin.: Celluvisc; Fr.:  Aquacel; Askina  Ampoules; Clip Clip Brulures; Comfeel; Comfeel; Hydrocoll; Hydrocoll; Physiotulle; Sureskin; Sureskin; Urgomed; Urgomed; Urgotul; Ger.:  Algoplaqu  Algoplaque; e; Alione; Cellufresh; Cellufresh; Cellumed; Cellumed; Celluvisc; Celluvisc; Comfeel Plus Transparenter; Physiotulle; Urgotul; Gr.: Cellufluid; Celluvisc; Hong Ho ng K ong: Refresh; Irl.: Celluvisc; Israel: Refresh Tears; Ital.: Cellufresh; Celluvisc; Lacrilens; Mal  Malays ays i a: Refresh Plus†; Refresh Tears†; Mex. : Celluvisc†; Novafix Ultra Fuerte; Refresh Liquigel; Refresh Tears; Thera Tears†; Neth.: Celluvisc; NZ: Cellufresh†; Celluvisc†; Refresh Tears Plus; Philipp.: Cellufresh; Celluvi Celluvisc; sc; Port.:  Aquacel†  Aquacel†;; Askina Biofilm†; Biofilm†; Cellufluid; Celluvisc; Celluvisc;  S .A fr fr.:.: Cellufresh; Celluvisc; Comfeel; Refresh Liquigel; Refresh Tears; S in ingg apore:

Celluvisc; Refresh Plus†; Refresh Tears†; S pain: Cellufresh; Celluvisc; Celluvisc; Viscofresh; S wed.: Celluvisc; S wi witz.: tz.: Cellufluid; Celluvisc; Thai.: Cellufresh; Celluvisc; UK: Celluvi Celluvisc; sc; Comfeel; Intrasite; Physiotulle Physiotulle;; USA: Celluvisc; Clear Eyes for Dry Eyes; Optive; Refresh Plus; Refresh Tears; Tears  Again; TheraTears; TheraTears; Venez.: Refresh Liquigel; Refresh Tears. Multi-ingredient: A r g .: Comfeel Plus; Comfeel Purilon†; Comfeel Sea Sorb†; Humectante Bucal; Mucobase; Purilon; Razagleda Plus†; Seasorb; Orabase; Orahesive†; SoloSite; SoloSite; Stomahesive†; Stomahesive†; A us tri  A us tral.:  Aquae; Orabase; tria: a: Glandosane; Sialin; Braz.: Chofranina; Canad.: Appedrine  Appedrine†; †; Carboflex†; Carboflex†; Orabase†; Orahesive†; Salivart; Tegasorb; Chile: Delgadol Fibra; K.C.M.C; Novafix Extra Fuerte; Reducform-F; Reducform-F; Salivart†; Cz.:  Alginete†; Spofax; Spofax; Fr.:  Altreet Ag; Amivia†; Amivia†; Aquacel Ag; Artisial; Artisial; Askina Sorb†; Sorb†; Biatain Argent; Argent; Cellosorb; Clip Hemo; Intrasite; Melgisorb; Purilon; Release Ag; Seasorb; Urgosorb; Urgotul S.Ag; Ger.: Cellosorb; Comfeel Plus; Glandosane; LaryPhary; Nu-Gel†; Nu-Gel†; Purilon; Recatol Algin; SeaSorb Soft; Ho Hong ng K on ong: g:  Aquae; Glandosane; Salivart; India: Digene; Irl.: Orabase; Israel: Orabase†; Ital.:  Aquacel Ag; NZ: Orabase; Stomahesiv Stomahesive; e; Port.: Askina Sorb†; Carboflex†; Carboflex†; Glandosane; Varihesive†; S .A fr fr.:.: Granuflex; Granugel; Orabase; S pain: Laxvital; S wi witz.: tz.: Glandosane; Thai.: Bisolax; Emulax; Glandosane†; UK: Comfeel Plus; Glandosane; Luborant; Orabase; Orahesive; Physiotulle-Ag; SeaSorb Soft; Seprafilm; Stomahesive; Stomahesive; USA: Entertainer’s Secret; Moi-Stir; Moi-Stir; Pretts Diet Aid; Salivart; Seprafilm; Surgel; Venez.: Klincosal; Novafix; Polantac.