TOIMINTAUNITA USON 20180071390A1ULLA LA MUNGUKURTI | ( 19) United States (12 ) Patent Application Publication (10 ) Pub. No. : US 2018/ 0071390 A1 PATEL et al. (43 ) Pub . Date : Mar . 15 , 2018 ( 54 ) COMPOSITIONS OF PHARMACEUTICAL A61K 9 / 06 (2006 .01 ) ACTIVES CONTAINING DIETHYLENE A61K 9 /00 (2006 .01 ) GLYCOL MONOETHYL ETHER OR OTHER A61K 31 /573 ( 2006 .01 ) ALKYL DERIVATIVES A61K 31/ 565 ( 2006 .01 ) A61K 31/ 4439 ( 2006 . 01 ) ( 71 ) Applicant : THEMIS MEDICARE LIMITED , A61K 31 / 167 ( 2006 . 01 ) Mumbai (IN ) A61K 31 / 57 (2006 . 01) (52 ) U . S . CI. (72 ) Inventors : Dinesh Shantilal PATEL , Mumbai CPC .. .. .. A61K 47 / 10 ( 2013 . 01 ) ; A61K 9 /4858 ( IN ) ; Sachin Dinesh PATEL , Mumbai ( 2013 .01 ) ; A61K 9 /08 ( 2013 .01 ) ; A61K 9 / 06 ( IN ) ; Shashikant Prabhudas ( 2013 .01 ) ; A61K 9 / 0014 ( 2013 .01 ) ; A61K KURANI, Mumbai ( IN ) ; Madhavlal 31/ 573 ( 2013 .01 ) ; A61K 31 /57 ( 2013 .01 ) ; Govindlal PATEL , Mumbai ( IN ) A61K 31/ 565 ( 2013 .01 ) ; A61K 31 /4439 (73 ) Assignee : THEMIS MEDICARE LIMITED , ( 2013 .01 ) ; A61K 31/ 167 ( 2013 .01 ) ; A61K Mumbai (IN ) 9 /0048 ( 2013 .01 ) ; A61K 9 /0019 (2013 .01 ) ( 57 ) ABSTRACT (21 ) Appl. No .: 15 / 801, 390 The present invention relates to pharmaceutical composi tions of various pharmaceutical actives, especially lyophilic ( 22 ) Filed : Nov . 2 , 2017 and hydrophilic actives containing Diethylene glycol mono ethyl ether or other alkyl derivatives thereof as a primary Related U . S . Application Data vehicle and /or to pharmaceutical compositions utilizing (62 ) Division of application No. 14 /242 , 973 , filed on Apr. Diethylene glycol monoethyl ether or other alkyl derivatives 2 , 2014 , now Pat. No. 9 , 827 ,315 . thereof as a primary vehicle or as a solvent system in preparation of such pharmaceutical compositions . The phar (30 ) Foreign Application Priority Data maceutical compositions of the present invention are safe , non - toxic , exhibits enhanced physical stability compared to Apr. 2 , 2013 ( IN ) .. .. .. 1287 /MUM / 2013 conventional formulations containing such pharmaceutical actives and are suitable for use as injectables for intravenous Publication Classification and intramuscular administration , as well as for use as a (51 ) Int. Ci. preformed solution / liquid for filling in and preparation of A61K 47 / 10 ( 2006 .01 ) capsules, tablets , nasal sprays, gargles , dermal applications , A61K 9 / 48 ( 2006 .01 ) gels , topicals , liquid oral dosage forms and other dosage A61K 9 / 08 ( 2006 .01 ) forms. Patent Application Publication Mar . 15 , 2018 US 2018 /0071390 A1 Figure 1 : Sensor application method at injection site US 2018 /0071390 A1 Mar. 15 , 2018 COMPOSITIONS OF PHARMACEUTICAL [0010 ] VI) Hypnotic Agents ; ACTIVES CONTAINING DIETHYLENE [ 0011 ] VII ) Antifungal Agents ; GLYCOL MONOETHYL ETHER OR OTHER [0012 ] VIII ) Oxicams; ALKYL DERIVATIVES [0013 ]. IX ) ACE Inhibitors ; 0014 ) X ) Muscle Relaxants ; CROSS REFERENCE APPLICATIONS [0015 ]. XI) Antibiotics ; [0016 ] XII) Aldosterone Receptor Antagonists ; [0001 ] This application is a Divisional of U . S . Ser . No . [0017 ] XIII ) Cardiovascular Agents ; 14 / 242 ,973 filed Apr. 2 , 2014 which claims the benefit of [0018 ] XIV ) Calcium Channel Blockers ; Indian Application No . 1287 /MUM / 2013 filed Apr. 2 , 2013 , [00191 . XV ) Anti - arrhythmic Agents ; the content of which is incorporated by reference . [ 0020 ] XVI) Cardiac Glycosides and other Drugs related to CVS ; FIELD OF THE INVENTION 10021] XVII) Antipsychotic Agents ; [0002 ] The present invention relates to pharmaceutical [ 0022 ] XVIII ) Anticonvulsants ; compositions of various pharmaceutical actives containing [0023 ]. XIX ) Diuretics ; Diethylene glycolmonoethyl ether or other alkyl derivatives [ 0024 ] XX ) Anticancer Agents ; thereof as a primary vehicle and / or to pharmaceutical com [0025 ] XXI) Immunosuppressants ; positions utilizing Diethylene glycol monoethyl ether or [ 0026 ] XXII ) Vitamins and Minerals ; and other alkyl derivatives thereof as a primary vehicle or as a [ 0027 ] XXIII ) Peptides solvent system in preparation of such pharmaceutical com [0028 ] In the past , numerous agents have been used to positions. The present invention especially relates to phar solubilize various categories of drugs. The use of organic maceutical compositions of lipophilic and hydrophilic solvents like Acetone , Methanol, Ethyl acetate , Tetrahydro actives containing Diethylene glycol monoethyl ether or furan , Chloroform , Hexane , etc . , for their subsequent use other alkyl derivatives thereof as a primary vehicle and /or to either as oral or injectable ( intramuscularly or intravenously ) pharmaceutical compositions utilizing Diethylene glycol is prohibited . monoethyl ether or other alkyl derivatives thereof as a [0029 ] Use of oil and its derivatives has its limitations as primary vehicle or as a solvent system in preparation of such these are derived from plant origin like sesame oil, cotton pharmaceutical compositions . The pharmaceutical compo seed oil etc ., which poses stability problems because their sitions of the present invention are safe , non - toxic , exhibits quality changes with season , may get unstable / rancid as well enhanced physical stability compared to conventional for as their bulky viscous nature result in pain and further mulations containing such pharmaceutical actives and are complication during application at the injecting site . suitable for use as injectables for intravenous and intramus [ 0030 ] Manufacture of injectables using oil and its deriva cular administration , as well as for use as a preformed tive also leads to problems from a quality control point of solution / liquid for filling in and preparation of capsules , view . The tendencies of seasonal changes in oil quality tablets , nasal sprays , gargles , dermal applications, gels , ( rancidity ) and color change were problems encountered by topicals , liquid oral dosage forms and other dosage forms. manufacturing chemists . The pesticide residue from oil of BACKGROUND OF THE INVENTION natural origin is a potential risk factor for injectable forms. Further sterilization and difficulties during filtration are the [ 0003 ] Formulation of various pharmaceutical actives , added secondary problems. especially lipophilic actives is a problem because many such 10031 ] Use of emulsions for solubilizing various drugs actives are difficult to solubilize , by virtue of their poor was also attempted . But the stability of emulsions, its solubility ; because many formulations containing such particle size and sterility resulted in high cost of production . actives have poor stability and hence are difficult to manu Moreover, various technologies are developed for adminis facture and in many instances require such formulations to tration in the injectable form and also pose the problems of be lyophilized or freeze dried ; and because many formula pain at the site of the injection . tions containing such actives are required to be formulated 10032 ] The abovementioned factors limit the use of oil as as emulsions and hence difficult to manufacture . This is well as oil /water emulsions as solubilizing agents for the especially true for formulations of such actives in the form preparation of various categories of active drugs . Moreover, of injectables , capsules, gargles, solutions etc and other some of the derivatives of oil cause anaphylactic shocks and dosage forms. Preparation of various lipophilic drugs that histamine release , thus reducing their usage . are poorly soluble or insoluble in water/ other solvents in [0033 ] The use of fatty acids and its derivative also soluble pellucid has been a continuing problem in the art . requires special quality control and their therapeutic use in [0004 ] Examples of such pharmaceutical actives, useful in oral and injectable forms are therefore limited . Use of various physiological conditions to alleviate the pathology polyethylene glycol derivatives are quite high but there are caused due to various disease conditions are the following , limitations to their use as they can be administered up to which are not restrictive and a person of skill in the art may certain levels only and are toxic at higher levels . Thus they select other compounds which fall into the aforementioned become specific either for oral or local applications and their categories: use is limited in injectables. [0005 ] I) Steroids and Hormones; 0034 ] Further , the problems associated with oil -based [ 0006 ] II ) Antimalarial agents ; injections are many, such as for instance a small test dose [0007 ] III ) Proton Pump Inhibitors ; prior to actual administration is usually required to confirm [ 0008] IV ) Analgesic Agents (NSAIDs and Narcotic Anal tolerability of both active and oily vehicle ; it causes pain , gesics ) ; erythema and swelling at the site of injection ; it leads to [0009 ] V ) COX 2 Inhibitors ; nodule formation at the site of injection ; it is associated with US 2018 /0071390 A1 Mar. 15 , 2018 a risk of damage to nerves , arteries or veins if improperly [0041 ] Thus the formulation of a clear solution of drugs given or administered ; if side effects occur they would be for therapy has always been challenge with the need of a prolonged until plasma levels fall — hence the necessity for solubilizer to give clear solution . a test dose ; it can take several weeks for plasma levels to [0042 ] It is known that ethanol is often used in varying reach steady state ; injection technique competency