Synthesis yeHydroxypropyl Methyl Cellulose Acetate uye Propionate

Kushandisa hydroxypropyl methylcellulose (HPMC) seyakabikwa, acetic anhydride uye propionic anhydride se esterification agents, iyo esterification reaction mu pyridine yakagadzirira hydroxypropyl methylcellulose acetate uye hydroxypropyl methylcellulose Cellulose propionate. Nekushandura huwandu hwekunyungudutsa hunoshandiswa muhurongwa, chigadzirwa chine zvivakwa zviri nani uye dhigirii rekutsiva chakawanikwa. Iyo yekutsiva dhigirii yakatemerwa netitration nzira, uye chigadzirwa chakaratidzirwa uye chakaedzwa kuita. Mhedzisiro yacho yakaratidza kuti reaction system yakaitwa pa110°C ye 1-2.5 h, uye mvura yakasvibiswa yakashandiswa semumiriri wemvura mushure mekuita, uye zvigadzirwa zvehupfu zvine dhigirii rekugadzirisa kupfuura 1 (inoretical degree of substitution yaiva 2) inogona kuwanikwa. Iyo ine yakanaka solubility mune akasiyana organic solvents senge ethyl ester, acetone, acetone / mvura, nezvimwe.

Mazwi akakosha: hydroxypropyl methylcellulose; hydroxypropyl methylcellulose acetate; hydroxypropyl methylcellulose propionate

Hydroxypropylmethylcellulose (HPMC) is a non-ionic polymer compound uye cellulose ether ine zvakawanda zvekushandisa. Seyakanakisa kemikari yekuwedzera, HPMC inowanzoshandiswa munzvimbo dzakasiyana siyana uye inonzi "industrial monosodium glutamate". Hydroxypropyl methylcellulose (HPMC) haina chete yakanaka emulsifying, thickening, uye kusunga mabasa, asiwo inogona kushandiswa kuchengetedza mwando uye kudzivirira colloids. Inoshandiswa zvakanyanya muminda yakawanda yakadai sechikafu, mishonga, machira, machira, uye zvekurima. . Kugadziriswa kwehydroxypropyl methylcellulose kunogona kushandura zvimwe zvezvivakwa zvayo, kuitira kuti zvigone kushandiswa zvirinani mune imwe ndima. Iyo molecular formula ye monomer yayo ndeye C10H18O6.

Mumakore achangopfuura, kutsvagisa nezve hydroxypropyl methylcellulose derivatives zvishoma nezvishoma yave nzvimbo inopisa. Nekugadzirisa hydroxypropyl methylcellulose, zvakasiyana-siyana zvinotorwa kubva kune zvakasiyana zvivakwa zvinogona kuwanikwa. Semuenzaniso, kuiswa kweacetyl mapoka kunogona kuchinja kushanduka kwemafirimu ekuputira ezvokurapa.

Kugadziriswa kwehydroxypropyl methylcellulose kunowanzoitwa pamberi peiyo acid catalyst yakadai seyakaomeswa sulfuric acid. Kuedza kunowanzoshandisa acetic acid sechinhu chinonyungudutsa. Mamiriro ekuita anonetsa uye anotora nguva, uye chigadzirwa chinoguma chine yakaderera dhigirii yekutsiva. (pasi pe1).

Mupepa iri, acetic anhydride uye propionic anhydride yakashandiswa se esterification agents kugadzirisa hydroxypropyl methylcellulose kugadzirira hydroxypropyl methylcellulose acetate uye hydroxypropyl methylcellulose propionate. Nekuongorora mamiriro akadai sekusarudzwa kwe solvent (pyridine), solvent dosage, nezvimwewo, zvinotarisirwa kuti chigadzirwa chine zvinhu zviri nani uye dhigirii rekutsiva chinogona kuwanikwa kuburikidza nenzira iri nyore. Mupepa iri, kuburikidza nekuongorora kwekuedza, chigadzirwa chakanangwa chine upfu uye dhigirii yekutsiva yakakura kupfuura 1 yakawanikwa, iyo yakapa humwe hutungamiriri hwedzidziso yekugadzirwa kwehydroxypropyl methylcellulose acetate uye hydroxypropyl methylcellulose propionate.

1. Chikamu chekuedza

1.1 Zvishandiso uye reagents

Pharmaceutical grade hydroxypropyl methylcellulose (KIMA CHEMICAL CO.,LTD, 60HD100, methoxyl mass fraction 28% -30%, hydroxypropoxyl mass fraction 7% -12%); acetic anhydride, AR, Sinopharm Group Chemical Reagent Co., Ltd.; Propionic Anhydride, AR, West Asia Reagent; Pyridine, AR, Tianjin Kemiou Chemical Reagent Co., Ltd.; methanol, ethanol, ether, ethyl acetate, acetone, NaOH uye HCl inowanikwa mune zvekutengesa analytically pure.

KDM thermostat electric heat mantle, JJ-1A kukurumidza kuyera dijitari inoratidza electric stirrer, NEXUS 670 Fourier shandura infrared spectrometer.

1.2 Kugadzirira kwehydroxypropyl methylcellulose acetate

Imwe chiyero che pyridine yakawedzerwa mumoto wemitsipa mitatu, uye ipapo 2.5 g ye hydroxypropyl methylcellulose yakawedzerwa ipapo, zvinogadzirisa zvakamutswa zvakaenzana, uye tembiricha yakasimudzwa kusvika 110.°C. Wedzera 4 mL yeacetic anhydride, ita pa110°C kweawa 1, kumisa kudziyisa, kutonhora kusvika kukamuri tembiricha, wedzera huwandu hwemvura yakasvibiswa kuti iwedzere chigadzirwa, sefa nekusveta, geza nemvura yakasvibiswa kakati wandei kusvika iyo eluate isingarereki, uye womisa chigadzirwa chengetedza.

1.3 Kugadzirira kwehydroxypropyl methylcellulose propionate

Imwe chiyero chepyridine yakawedzerwa mubhokisi rine mitsipa mitatu, uye ipapo 0.5 g ye hydroxypropyl methylcellulose yakawedzerwa ipapo, zvinogadzirisa zvakamutswa zvakaenzana, uye tembiricha yakasimudzwa kusvika 110.°C. Wedzera 1.1 mL yepropionic anhydride, ita pa110°C kwemaawa 2.5, kumisa kudziyisa, kutonhora kusvika kukamuri tembiricha, wedzera huwandu hwemvura yakasvibiswa kuti iwedzere chigadzirwa, sefa nekusveta, geza nemvura yakashambidzwa kakati wandei kusvika iyo eluate iri yepakati pfuma, chengetedza chigadzirwa chakaoma.

1.4 Kutemerwa kweiyo infrared spectroscopy

Iyo hydroxypropyl methylcellulose, hydroxypropyl methylcellulose acetate, hydroxypropyl methylcellulose propionate uye KBr zvakasanganiswa uye pasi zvakateerana, uye ndokutsikirirwa mumapiritsi kuti aone infrared spectrum.

1.5 Kutemerwa kwedhigirii rekutsiva

Gadzirira mhinduro dzeNaOH neHCl dzine huwandu hwe 0.5 mol/L, uye ita calibration kuti uone kunyatsoiswa; kuyera 0.5 g yehydroxypropylmethylcellulose acetate (hydroxypropylmethylcellulose propionic acid ester) mu250 mL Erlenmeyer flask, wedzera 25 mL yeacetone uye 3 madonhwe ephenolphthalein chiratidzo, sanganisa zvakanaka, wobva wawedzera 25 mL yeNaOH magineti yekuvhenganisa neelectromagnetic solution, NaOH magineti. 2 h; titrate neHCI kusvikira ruvara rutsvuku rwemhinduro ruchinyangarika, rekodha Ivhoriyamu V1 (V2) yehydrochloric acid inopedzwa; shandisa nzira imwechete kuyera vhoriyamu V0 yehydrochloric acid inopedzwa nehydroxypropyl methylcellulose, uye kuverenga dhigirii yekutsiva.

1.6 Solubility kuyedza

Tora huwandu hwakakodzera hwezvigadzirwa zvekugadzira, wozviwedzera kune organic solvent, zunza zvishoma, uye tarisa kuparara kwechinhu.

2. Migumisiro uye Hurukuro

2.1 Mhedzisiro yehuwandu hwepyridine (solvent)

Migumisiro yehuwandu hwakasiyana hwepyridine pane morphology yehydroxypropylmethylcellulose acetate uye hydroxypropylmethylcellulose propionate. Kana huwandu hwe solvent hushoma, huchaderedza kuwedzera kweketani ye macromolecular uye viscosity yehurongwa, kuitira kuti dhigirii ye esterification yemaitiro ekugadzirisa ideredzwe, uye chigadzirwa chichave chakasvibiswa sehuwandu hukuru. Uye kana huwandu hwekunyungudutsa hwakanyanya kuderera, reactant iri nyore kunyunguduka kuita bundu uye kunamatira kumadziro emidziyo, izvo zvisiri izvo chete zvisina kunaka pakuita kwekuita, asi zvakare zvinokonzeresa kukanganisa kukuru kurapwa mushure mekuita. . Muchigadzirwa che hydroxypropyl methylcellulose acetate, chiyero che solvent chinoshandiswa chinogona kusarudzwa se 150 mL / 2 g; nokuda kwekugadzirwa kwehydroxypropyl methylcellulose propionate, inogona kusarudzwa se80 mL / 0.5 g.

2.2 Infrared spectrum analysis

Infrared kuenzanisa chati ye hydroxypropyl methylcellulose uye hydroxypropyl methylcellulose acetate. Kuenzaniswa neyakagadzirwa, iyo infrared spectrogram yechigadzirwa hydroxypropyl methylcellulose acetate ine shanduko iri pachena. Mune infrared spectrum yechigadzirwa, peak yakasimba yakaonekwa pa 1740cm-1, ichiratidza kuti boka re carbonyl rakagadzirwa; uyezve, kusimba kweiyo kutambanudza kudengenyeka kwepamusoro kweOH pa 3500cm-1 yakanga yakaderera zvikuru kupfuura iyo yakasvibiswa, iyo yakaratidzawo kuti -OH Paiva nekuita.

Iyo infrared spectrogram yechigadzirwa hydroxypropyl methylcellulose propionate yakachinjawo zvakanyanya kana ichienzaniswa neyakagadzirwa. Mune infrared spectrum yechigadzirwa, peak yakasimba yakaonekwa pa 1740 cm-1, ichiratidza kuti boka re carbonyl rakagadzirwa; uyezve, iyo OH inotambanudza vibration peak intensity pa 3500 cm-1 yaive yakaderera zvakanyanya pane iyo yakabikwa, iyo yakaratidzawo kuti OH yakaita.

2.3 Kutemerwa kwedhigirii rekutsiva

2.3.1 Kutemerwa kwekutsiva dhigirii rehydroxypropyl methylcellulose acetate

Sezvo hydroxypropyl methylcellulose ine maviri OH muchikamu chimwe nechimwe, uye cellulose acetate chigadzirwa chinowanikwa nekutsiva imwe COCH3 yeH mune imwe OH, iyo theoretical yakanyanya degree yekutsiva (Ds) ndeye 2.

2.3.2 Kutemerwa kwedhigirii rekutsiva hydroxypropyl methylcellulose propionate

2.4 Solubility yechigadzirwa

Izvo zvinhu zviviri zvakasanganiswa zvaive zvakafanana solubility hunhu, uye hydroxypropyl methylcellulose acetate yaive yakanyungudika zvishoma pane hydroxypropyl methylcellulose propionate. Chigadzirwa chekugadzira chinogona kunyungudutswa muacetone, ethyl acetate, acetone / mvura yakasanganiswa solvent, uye ine sarudzo yakawanda. Mukuwedzera, hunyoro huri muacetone / mvura yakasanganiswa solvent inogona kuita kuti zvinyorwa zve cellulose zvive zvakachengeteka uye zvakatipoteredza kana zvichishandiswa sezvinhu zvekuputira.

3. Mhedziso

(1) Mamiriro ekugadzirwa kwehydroxypropyl methylcellulose acetate ndeaya anotevera: 2.5 g yehydroxypropyl methylcellulose, acetic anhydride seye esterification agent, 150 mL yepyridine sechinhu chinonyungudutsa, kupisa kwekuita pa110.° C, uye nguva yekuita 1h.

(2) Mamiriro ekugadzirwa kwehydroxypropyl methylcellulose acetate ndeaya: 0.5 g yehydroxypropyl methylcellulose, propionic anhydride se esterification agent, 80 mL yepyridine se solvent, reaction tembiricha pa110.°C, uye nguva yekuita 2 .5 h.

(3) Mishonga ye cellulose inogadzirwa pasi pechiitiko ichi yakananga mumhando yehupfu hwakatsetseka ine dhigirii yakanaka yekutsiva, uye izvi zviviri zvinobva kune cellulose zvinogona kunyungudutswa mune zvakasiyana organic zvinonyungudutsa senge ethyl acetate, acetone, uye acetone / mvura.