{"id":6190,"date":"2022-09-18T12:23:08","date_gmt":"2022-09-18T07:53:08","guid":{"rendered":"http:\/\/arasto.com\/product\/loratadine\/"},"modified":"2023-05-08T14:50:12","modified_gmt":"2023-05-08T11:20:12","slug":"loratadine","status":"publish","type":"product","link":"https:\/\/arasto.com\/fa\/product\/loratadine\/","title":{"rendered":"Loratadine"},"content":{"rendered":"

Description<\/strong><\/p>\n

(USP 44)<\/p>\n

    \n
  1. Drug Substance General Information (ICH 3.2.S.1)<\/strong><\/li>\n<\/ol>\n

    1.1. Nomenclature (ICH 3.2.S.1.1)<\/strong><\/p>\n

    International non-Proprietary Name: Loratadine (Brand Name: Claritine, Clarityn, Lisino)<\/p>\n

    Compendial Name: Loratadine<\/p>\n

    Chemical Name: Ethyl 4-(8-Chloro-5, 6-dihydro-11H-benzo [5, 6] cyclohepta [1, 2-b] pyridin-11- ylidene)-1-piperidinecarboxylate<\/p>\n

    Arasto\u2019s code: LOR<\/p>\n

    <\/a> CAS Registry Number: [79794-75-5]<\/p>\n

     <\/p>\n

      \n
    1. Drug Substance General Information (ICH 3.2.S.1)<\/strong><\/li>\n<\/ol>\n

      \u00a01.2. Structure (ICH 3.2.S.1.2)<\/strong><\/p>\n

      <\/p>\n

      Empirical Formula: C22<\/sub>H23<\/sub>ClN2<\/sub>O2<\/sub><\/p>\n

      <\/a> Molecular Weight: 382.88 g\/mol<\/p>\n

        \n
      1. Drug Substance General Information (ICH 3.2.S.1)<\/strong><\/li>\n<\/ol>\n

        \u00a0 1.3. General Properties (ICH 3.2.S.1.3)<\/strong><\/p>\n

        Loratadine is a white to off-white crystalline substance. It is administered orally for the treatment of symptoms of seasonal\u00a0allergic rhinitis<\/a>\u00a0and for the treatment of\u00a0chronic<\/a>idiopathic<\/a>urticaria<\/a>.\u00a0 It is practically insoluble in water and slightly soluble in 0.1 M HCl (4.1 mg\/ml at 25\u00b0C due to salt formation at the pyridine moiety), but highly soluble in most polar organic solvent except saturated hydrocarbons.\u00a0 It has a pKa<\/sub>\u00a0of 5 (http:\/\/druginfosys.com\/Drug.aspx?drugCode=428 &drugName=&type=0<\/a>) and a log P of 3.65 (http:\/\/pharmacycode.com\/Loratadine.html<\/a>). Loratadine is relatively stable to acid and base (see Stability Studies). Oral LD50<\/sub>\u00a0of Loratadine has been reported to be orally> 2000 mg\/kg in the rat (http:\/\/web.ncifcrf.gov\/rtp<\/a>\/LASP\/intra\/forms\/msds\/msds_Loratadine).<\/p>\n

        The determination of purity and assay of APIs require comparison of the product with their respective Reference Standards (RS) and Related Compounds (RC or known impurities).\u00a0 Accordingly, ICH regulations on the purity and assay of reference standard and related compounds are clearly defined and must be followed by drug substance and drug product manufacturers.<\/p>\n

        According to ICH Q7, 11.1 there are 3 types of standards.\u00a0 This is summarized in the following chart and discussed in detail below.<\/p>\n

        <\/p>\n

         <\/p>\n

        The impurities provided in the following table represent Secondary Reference Standards (SRS) that are prepared in-house by synthesis or by isolation.\u00a0 Each SRS has undergone extensive characterization (IR, UV, 1HNMR, 13CNMR. Mass Spec) and determination of its purity and assay (HPLC).\u00a0 For specification of the SRS of those products that have a monograph, the SRS is compared with a pharmacopoeia Primary Reference Standard (UV, HPLC retention time).\u00a0 For specification of those products that do not have a monograph (known as House Primary Standard), we compare their UV \u03b5 or \u05d2\/max<\/sub>, IR major absorptions, 1<\/sup>HNMR d (ppm), 13<\/sup>CNMR d (ppm) or HPLC retention time with values reported in the chemical literature for these compounds.<\/p>\n

        <\/strong><\/p>\n

          \n
        1. Primary and Secondary Reference Standard (ICH 3.2.S.5)<\/strong><\/li>\n<\/ol>\n

          5.1.\u00a0Active Pharmaceutical Ingredient<\/strong><\/p>\n

          Primary Reference Standard for Loratadine is available from United States Pharmacopoeia. We will use a Secondary Reference Standard (previously referred to as Working Standard) for direct control of all batches of Loratadine.<\/p>\n

          As per ICH (Q7, 11.1) and ICH (Q6, 2.11, 3.2, 3.3) the Secondary Reference Standards, which include the API and its Related Compounds,\u00a0must be examined for their proof of structure (characterization), assay and purity and specification (identification by comparison). Furthermore, ICH Guideline on the Preparation of Common Technical Document (Q4M) requires that the data obtained from characterization, assay and purity and specification must be included in section 3.2.S.3.2 for Related Compounds (already discussed in that section) and section 3.2.S.5 of the DMF for the API.\u00a0To this end, the Secondary Reference Standards of the API Loratadine has undergone extensive characterization (UV, IR,\u00a01<\/sup>\u00a0H NMR,\u00a013<\/sup>C NMR, Mass Spec) to assure its structure, assay and purity (HPLC and\/or titration) and specification (comparison of its HPLC retention time and UV \u05d2\/max<\/sub>\u00a0with USP Primary Reference Standard.<\/p>\n

          The Secondary Reference Standard for Loratadine was produced from a released batch of Loratadine by subjecting it to an additional crystallization from the final solvent system used in the production of the API to avoid the possibility of other polymorph formation.<\/p>\n

          SPECIFICATION OF ANALYSIS<\/h1>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
          Product:<\/strong> Loratadine<\/td>\nCAS No:<\/strong> 79794-75-5<\/td>\nSpec. No.: <\/strong>APC-QC-SPEC-383-00<\/td>\n<\/tr>\n
          Issue Date: <\/strong>Apr, 2023<\/td>\nValid up to:<\/strong> Apr, 2024<\/td>\nReference: <\/strong>USP44<\/td>\n<\/tr>\n
          Tests<\/strong><\/td>\n\n

          Specifications<\/h2>\n<\/td>\n<\/tr>\n

          Description<\/td>\nWhite to off-white powder.<\/td>\n<\/tr>\n
          Solubility<\/td>\nFreely soluble in acetone, in chloroform, in methanol, and in toluene, insoluble in water.<\/td>\n<\/tr>\n
          Identification<\/td>\nA: Infrared Spectroscopy<\/p>\n

          B: The retention time of the major peak of the sample solution corresponds to that of the Standard Solution, as obtained in the Assay.<\/td>\n<\/tr>\n

          Loss on drying<\/td>\nNMT 0.5%<\/td>\n<\/tr>\n
          Residue on ignition<\/td>\nNMT 0.1%<\/td>\n<\/tr>\n
          Residual Solvents<\/td>\nMethanol: NMT 3000 ppm (Class II)<\/p>\n

          Toluene: NMT 890 ppm (Class II)<\/td>\n<\/tr>\n

          Organic Impurities ;Procedure 2 (HPLC)<\/td>\nLoratadine related compound A: NMT 0.1%<\/p>\n

          Loratadine related compound B: NMT 0.1%<\/p>\n

          Loratadine related compound C: NMT 0.1%<\/p>\n

          Hydroxyl deacyl analog: NMT 0.1%<\/p>\n

          Dichlorobenzocycloheptapyridinone: NMT 0.1%<\/p>\n

          Hydroxyloratadine: NMT 0.1%<\/p>\n

          4-Chloroloratadine: NMT 0.1%<\/p>\n

          Any individual unknown impurity: NMT 0.10%<\/p>\n

          Total impurities: NMT. 0.3%<\/td>\n<\/tr>\n

          Assay (HPLC)<\/td>\n98.5% to 101.0% (on the dried basis)<\/td>\n<\/tr>\n
          Prepared by:<\/strong> M. Shahbazi, B.Sc.Chem.<\/td>\nChecked by:<\/strong> A. Forghani, B.Sc.Chem.<\/td>\n<\/tr>\n
          Approved by:<\/strong> F. Javadizadeh, M.Sc.Chem.<\/td>\n<\/tr>\n
          Storage:<\/strong> Preserve in well-closed containers, and store between 2\u00b0 and 30\u00b0.<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n","protected":false},"excerpt":{"rendered":"

          Description (USP 44) Drug Substance General Information (ICH 3.2.S.1) 1.1. Nomenclature (ICH 3.2.S.1.1) International non-Proprietary Name: Loratadine (Brand Name: Claritine, Clarityn, Lisino) Compendial Name: Loratadine Chemical Name: Ethyl 4-(8-Chloro-5, 6-dihydro-11H-benzo [5, 6] cyclohepta [1, 2-b] pyridin-11- ylidene)-1-piperidinecarboxylate Arasto\u2019s code: LOR CAS Registry Number: [79794-75-5]   Drug Substance General Information (ICH 3.2.S.1) \u00a01.2. Structure (ICH 3.2.S.1.2) […]<\/p>\n","protected":false},"featured_media":7988,"comment_status":"closed","ping_status":"closed","template":"","meta":[],"product_cat":[72],"product_tag":[],"class_list":["post-6190","product","type-product","status-publish","has-post-thumbnail","hentry","product_cat-72"],"_links":{"self":[{"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product\/6190","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product"}],"about":[{"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/types\/product"}],"replies":[{"embeddable":true,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/comments?post=6190"}],"version-history":[{"count":1,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product\/6190\/revisions"}],"predecessor-version":[{"id":7990,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product\/6190\/revisions\/7990"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/media\/7988"}],"wp:attachment":[{"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/media?parent=6190"}],"wp:term":[{"taxonomy":"product_cat","embeddable":true,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product_cat?post=6190"},{"taxonomy":"product_tag","embeddable":true,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product_tag?post=6190"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}