ʻO ka Hydroxypropyl methylcellulose (HPMC)
Māhele: nā mea uhi; Mea membrane; Nā mea polymer i kāohi ʻia ka wikiwiki no nā hoʻomākaukau hoʻokuʻu lohi; Mea hoʻopaʻa; Kōkua hoʻokuʻu, mea hoʻopili papa; Mea hoʻopili i hoʻoikaika ʻia.
1. Hoʻolauna huahana
He NON-IONIC CELLULOSE ETHER kēia HUAHANA, ʻike ʻia ma waho he pauka keʻokeʻo, ʻala ʻole a ʻono ʻole, hoʻoheheʻe ʻia i ka wai a me ka hapa nui o nā mea hoʻoheheʻe organik polar, pehu i ka wai anuanu i kahi hopena colloidal maopopo a ʻāwili iki paha. Loaʻa i ka hopena wai ka hana ʻili, transparency kiʻekiʻe a me ka hana paʻa. Loaʻa i ka HPMC ka waiwai o ka gel wela. Ma hope o ka hoʻomehana ʻana, hana ka hopena wai huahana i ka hoʻopulapula gel, a laila hoʻoheheʻe ma hope o ka hoʻomaʻalili ʻana. He ʻokoʻa ka mahana o ka gel o nā kikoʻī like ʻole. Hoʻololi ka solubility me ka viscosity, haʻahaʻa ka viscosity zhao, ʻoi aku ka nui o ka solubility, ʻokoʻa nā kikoʻī like ʻole o nā waiwai HPMC, ʻaʻole i hoʻopilikia ʻia ka HPMC i hoʻoheheʻe ʻia i ka wai e ka waiwai pH.
ʻO ka mahana kuni koke, ka nui o ka wehe ʻana, ka nui maoli a me ka mahana hoʻololi aniani he 360℃, 0.341g/cm3, 1.326g/cm3 a me 170 ~ 180℃, kēlā me kēia. Ma hope o ka hoʻomehana ʻana, lilo ia i ʻeleʻele ma 190 ~ 200 ° C a puhi ma 225 ~ 230 ° C.
ʻAneʻane hiki ʻole ke hoʻoheheʻe ʻia ka HPMC i loko o ka chloroform, ethanol (95%), a me ka diethyl ether, a hoʻoheheʻe ʻia i loko o ka hui ʻana o ka ethanol a me ka methylene chloride, kahi hui ʻana o ka methanol a me ka methylene chloride, a me kahi hui ʻana o ka wai a me ka ethanol. Hiki ke hoʻoheheʻe ʻia kekahi mau pae o ka HPMC i loko o nā hui ʻana o ka acetone, methylene chloride, a me 2-propanol, a me nā mea hoʻoheheʻe organik ʻē aʻe.
Papa 1: Nā ʻōkuhi loea
papahana
Ana,
60 gd (2910).
65GD(2906)
75GD(2208)
Methoxy %
28.0-32.0
27.0-30.0
19.0-24.0
% Hydroxypropoxy
7.0-12.0
4.0-7.5
4.0-12.0
Mahana gel ℃
56-64.
62.0-68.0
70.0-90.0
Ka mānoanoa (mpa s).
3,5,6,15,50,4000
50400 0
100400 0150 00100 000
Ka emi ʻana o ke kaumaha maloʻo %
5.0 a emi mai paha
Ke koena kuni %
1.5 a emi mai paha
pH
4.0-8.0
Metala kaumaha
20 a emi mai paha
ʻāsenika
2.0 a emi mai paha
2. Nā hiʻohiʻona huahana
2.1 Hoʻoheheʻe ʻia ka Hydroxypropyl methylcellulose i loko o ka wai anuanu e hana i kahi hopena colloidal viscous. Inā hoʻohui ʻia i ka wai anuanu a hoʻoulu iki ʻia, hiki ke hoʻoheheʻe ʻia i loko o kahi hopena moakaka. I ka ʻaoʻao ʻē aʻe, ʻaʻole ia e hoʻoheheʻe ʻia i ka wai wela ma luna o 60℃ a hiki ke pehu wale. I ka hoʻomākaukau ʻana o ka hopena wai hydroxypropyl methicellulose, ʻoi aku ka maikaʻi o ka hoʻohui ʻana i kahi hapa o ka hydroxypropyl methicellulose i loko o kahi nui o ka wai, hoʻoulu ikaika, hoʻomehana ʻia i 80 ~ 90℃, a laila hoʻohui i ke koena hydroxypropyl methicellulose, a laila e hoʻohana i ka wai anuanu e hoʻohui i ka nui e pono ai.
2.2 ʻO ka Hydroxypropyl methylcellulose kahi ether cellulose non-ionic, ʻaʻole lawe kāna hopena i ka uku ionic, ʻaʻole launa pū me nā paʻakai metala a i ʻole nā hui organik ionic, i mea e hōʻoia ai ʻaʻole e pane ka HPMC me nā mea maka ʻē aʻe a me nā excipients i ke kaʻina hana hoʻomākaukau.
2.3 Loaʻa i ka Hydroxypropyl methylcellulose ka anti-sensitivity ikaika, a me ka piʻi ʻana o ke kekelē pani i ke ʻano molekala, hoʻonui ʻia hoʻi ka anti-sensitivity. ʻOi aku ka paʻa o ke ʻano o nā lāʻau lapaʻau e hoʻohana ana i ka HPMC ma ke ʻano he excipients i loko o ka manawa kūpono ma mua o nā lāʻau lapaʻau e hoʻohana ana i nā excipients kuʻuna ʻē aʻe (starch, dextrin, powdered sugar).
2.4 He inert ka Hydroxypropyl methylcellulose i ka metabolism. Ma ke ʻano he mea hoʻohui lāʻau lapaʻau, ʻaʻole ia e metabolized a omo ʻia paha, no laila ʻaʻole ia e hāʻawi i ka wela i nā lāʻau lapaʻau a me ka meaʻai. Loaʻa iā ia kahi hoʻohana kūikawā i ka waiwai calorific haʻahaʻa, ʻaʻohe paʻakai, nā lāʻau lapaʻau ʻaʻole allergenic a me ka meaʻai no ka poʻe maʻi diabetes.
He kūpaʻa ka 2.5HPMC i nā waikawa a me nā kumu, akā inā ʻoi aku ka pH ma mua o 2 ~ 11 a ua hoʻopilikia ʻia e ke kiʻekiʻe o ka mahana a i ʻole ka manawa mālama lōʻihi, e hōʻemi ia i ke kiʻekiʻe o ka oʻo ʻana.
2.6 Hiki i ka hopena wai o ka Hydroxypropyl methylcellulose ke hāʻawi i ka hana ʻili, e hōʻike ana i nā waiwai o ka ʻili a me ka hoʻoluhi interfacial. Loaʻa iā ia kahi emulsification maikaʻi i ka ʻōnaehana ʻelua-phase a hiki ke hoʻohana ʻia ma ke ʻano he mea hoʻopaʻa maikaʻi a me ka colloid pale.
2.7 Loaʻa i ka wai hoʻoheheʻe wai Hydroxypropyl methylcellulose nā waiwai hana kiʻiʻoniʻoni maikaʻi loa, a he mea uhi maikaʻi ia no nā papa a me nā pila. ʻAʻohe kala a paʻakikī ka membrane i hana ʻia e ia. Inā hoʻohui ʻia ka glycerol, hiki ke hoʻonui ʻia kona plasticity. Ma hope o ka mālama ʻana i ka ʻili, hoʻopuehu ʻia ka huahana i loko o ka wai anuanu, a hiki ke hoʻomalu ʻia ka helu hoʻoheheʻe ma ka hoʻololi ʻana i ke kaiapuni pH. Hoʻohana ʻia ia i nā hoʻomākaukau hoʻokuʻu lohi a me nā hoʻomākaukau i uhi ʻia me ka enteric.
3. Hoʻopili huahana
3.1. Hoʻohana ʻia ma ke ʻano he mea hoʻopili a me ka mea hoʻoheheʻe
Hoʻohana ʻia ʻo HPMC e hoʻolaha i ka hoʻoheheʻe ʻana o ka lāʻau lapaʻau a me ke kekelē o ka hoʻokuʻu ʻana i nā noi, hiki ke hoʻoheheʻe pololei ʻia i loko o ka mea hoʻoheheʻe e like me ka mea hoʻopili. ʻO ka viscosity haʻahaʻa o HPMC i hoʻoheheʻe ʻia i ka wai e hana i kahi hopena colloid sticky ivory, nā papa, nā pila, nā granules ma luna o ka mea hoʻopili a me ka mea hoʻoheheʻe, a ʻo ka viscosity kiʻekiʻe no ka glue, hoʻohana wale ʻia ma muli o nā ʻano like ʻole a me nā koi like ʻole, ʻo ka laulā he 2% ~ 5%.
ʻO ka hopena wai HPMC a me kahi ʻano o ka ethanol e hana i kahi mea hoʻopaʻa hui; Laʻana: 2% HPMC hopena wai i hui pū ʻia me 55% hopena ethanol i hoʻohana ʻia no ka pelleting o nā capsules amoxicillin, no laila ua piʻi ka awelika o ka hoʻoheheʻe ʻana o nā capsules amoxicillin mai 38% a 90% me ka ʻole o HPMC.
Hiki ke hana ʻia ka HPMC me ka hoʻopili hui ʻia me ka nui like ʻole o ka slurry starch ma hope o ka hoʻoheheʻe ʻana; Ua piʻi ka hoʻoheheʻe ʻana o nā papa i uhi ʻia me ka erythromycin enteric mai 38.26% a i 97.38% i ka wā i hui pū ʻia ai ka 2% HPMC a me 8% starch.
2.2. Hana i nā mea uhi kiʻiʻoniʻoni a me nā mea hana kiʻiʻoniʻoni
ʻO HPMC ma ke ʻano he mea uhi wai-hoʻoheheʻe ʻia nā ʻano penei: ka mānoanoa o ka hopena kaulike; He maʻalahi ke kaʻina hana uhi; ʻOi aku ka maikaʻi o ka hana ʻana i ka ʻili; Hiki ke mālama i ke ʻano o ka ʻāpana, kākau; Hiki ke pale i ka makū; Hiki ke kala, hoʻoponopono i ka ʻono. HOʻOHANA ʻIA kēia HUAHANA MA KE ʻANO HE UHI ʻILI WAI-HOʻOHEʻE ʻIA NO NĀ PAPA A ME NĀ PILA ME KA VISCOSITY HAʻAHAʻA, A NO KA UHI ʻILI WAI ʻOLE ME KA VISCOSITY KIʻEKIʻE, ʻO KA NUI O KA HOʻOHANA HE 2%-5%.
2.3, ma ke ʻano he mea hoʻomānoanoa a me ka glue pale colloidal
ʻO ka HPMC i hoʻohana ʻia ma ke ʻano he mea hoʻomānoanoa he 0.45% ~ 1.0%, hiki ke hoʻohana ʻia e like me nā kulu maka a me nā mea hoʻomānoanoa waimaka artificial; Hoʻohana ʻia e hoʻonui i ke kūpaʻa o ka glue hydrophobic, pale i ka hui ʻana o nā ʻāpana a me ka ua, ʻo ka dosage maʻamau he 0.5% ~ 1.5%.
2.4, ma ke ʻano he mea pale, mea hoʻokuʻu lohi, mea hoʻokuʻu i kāohi ʻia a me ka mea pore
Hoʻohana ʻia ke kumu hoʻohālike viscosity kiʻekiʻe o HPMC e hoʻomākaukau i nā mea pale a me nā mea hoʻokuʻu i kāohi ʻia o nā mea i hui pū ʻia me nā papa hoʻokuʻu hoʻomau iwi a me nā papa hoʻokuʻu hoʻomau iwi gel hydrophilic. ʻO ke kumu hoʻohālike viscosity haʻahaʻa he mea hoʻoulu pore no nā papa hoʻokuʻu hoʻomau a i ʻole nā papa hoʻokuʻu i kāohi ʻia i hiki ke loaʻa koke ka mahele therapeutic mua o ia mau papa, a ukali ʻia e ka hoʻokuʻu hoʻomau a i ʻole ka hoʻokuʻu i kāohi ʻia e mālama i nā ʻano maikaʻi i loko o ke koko.
2.5. ʻO ka matrix gel a me ka suppository
Hiki ke hoʻomākaukau ʻia nā suppositories hydrogel a me nā hoʻomākaukau hoʻopili gastric ma ka hoʻohana ʻana i ke ʻano o ka hoʻokumu ʻana o ka hydrogel i hoʻohana pinepine ʻia e HPMC i ka wai.
2.6 Nā mea hoʻopili olaola
Ua hui pū ʻia ʻo Metronidazole me HPMC a me polycarboxylethylene 934 i loko o kahi mea hui e hana i nā papa hoʻokuʻu bioadhesive i hoʻomalu ʻia e loaʻa ana he 250mg. Ua hōʻike ka hoʻāʻo hoʻoheheʻe in vitro ua pehu koke ka hoʻomākaukau ʻana i ka wai, a ua kāohi ʻia ka hoʻokuʻu ʻana o ka lāʻau lapaʻau e ka hoʻolaha ʻana a me ka hoʻomaha ʻana o ke kaulahao kalapona. Ua hōʻike ka hoʻokō ʻana o nā holoholona he nui nā waiwai hoʻopili olaola o ka ʻōnaehana hoʻokuʻu lāʻau lapaʻau hou i ka mucosa sublingual bovine.
2.7, ma ke ʻano he kōkua hoʻokuʻu
ʻO ke viscosity KIʻEKIʻE o kēia huahana he mea kōkua maikaʻi ia no ka hoʻomākaukau ʻana i ka wai hoʻoheheʻe, ʻo kona nui maʻamau he 0.5% ~ 1.5%.
4. Nā laʻana noi
4.1 Wai hoʻoheheʻe ʻiliʻili: HPMC 2kg, talc 2kg, ʻaila castor 1000ml, Twain -80 1000ml, propylene glycol 1000ml, 95% ethanol 53000ml, wai 47000ml, ka nui kūpono o ka pigment. ʻElua ala e hana ai.
4.1.1 Ka hoʻomākaukau ʻana i ka wai lole i uhi ʻia i ka pigment hiki ke hoʻoheheʻe ʻia: E hoʻohui i ka nui i kuhikuhi ʻia o HPMC i loko o ka 95% ethanol, e hoʻomohu i ka pō, e hoʻoheheʻe i kahi vector pigment ʻē aʻe i loko o ka wai (e kānana inā pono), e hoʻohui i nā hopena ʻelua a hoʻoulu like e hana i kahi hopena moakaka. E kāwili i ka 80% o ka hopena (20% no ka poli ʻana) me ka nui i kuhikuhi ʻia o ka ʻaila castor, Tween-80, a me ka propylene glycol.
4.1.2 Hoʻomākaukau ʻia ka wai uhi pigment insoluble (e like me ka hao oxide) HPMC i hoʻomoʻa ʻia i loko o 95% ethanol i ka pō, a ua hoʻohui ʻia ka wai e hana i ka 2% HPMC moakaka. Ua lawe ʻia he 20% o kēia hopena no ka polishing, a ua hoʻomākaukau ʻia ke koena 80% hopena a me ka hao oxide ma ke ʻano wili wai, a laila ua hoʻohui ʻia ka nui o nā mea ʻē aʻe a hui like ʻia no ka hoʻohana ʻana. Ke kaʻina hana uhi o ka wai uhi: e ninini i ka pepa palaoa i loko o ka ipu uhi kō, ma hope o ka hoʻololi ʻana, e hoʻomehana mua ka ea wela i 45 ℃, hiki iā ʻoe ke pīpī i ka uhi hānai, kaohi kahe ma 10 ~ 15ml/min, ma hope o ka pīpī ʻana, e hoʻomau i ka maloʻo me ka ea wela no 5 ~ 10min hiki ke puka i waho o ka ipu, e hoʻokomo i loko o ka mea maloʻo e maloʻo no ka ʻoi aku ma mua o 8h.
Ua hoʻoheheʻe ʻia ka membrane maka 4.2α-interferon 50μg o ka α-interferon i loko o 10ml0.01ml hydrochloric acid, i hui pū ʻia me 90ml ethanol a me 0.5GHPMC, kānana ʻia, uhi ʻia ma luna o ke koʻokoʻo aniani wili, sterilized ma 60℃ a hoʻomaloʻo ʻia i ka lewa. Hana ʻia kēia huahana i mea ʻiliʻili.
4.3 Nā papa Cotrimoxazole (0.4g±0.08g) SMZ (80 mesh) 40kg, starch (120 mesh) 8kg, 3% HPMC wai hoʻonā 18-20kg, magnesium stearate 0.3kg, TMP (80 mesh) 8kg, ʻo ke ʻano hoʻomākaukau, ʻo ia ke kāwili ʻana iā SMZ a me TMP, a laila hoʻohui i ka starch a kāwili no 5min. Me ka wai hoʻonā 3% HPMC i hana mua ʻia, mea palupalu, me ka granulation pale 16 mesh, hoʻomaloʻo, a laila me ka palaoa holoʻokoʻa pale 14 mesh, hoʻohui i ka hui magnesium stearate, me nā papa hoʻopaʻa huaʻōlelo 12mm (SMZco). Hoʻohana nui ʻia kēia huahana ma ke ʻano he mea hoʻopaʻa. ʻO ka hoʻoheheʻe ʻana o nā papa he 96%/20min.
4.4 Nā papa Piperate (0.25g) piperate 80 mesh 25kg, starch (120 mesh) 2.1kg, magnesium stearate ka nui kūpono. ʻO kāna ʻano hana, ʻo ia ke kāwili like ʻana i ka waikawa pipeoperic, starch, HPMC, me 20% mea palupalu ethanol, 16 mesh screen granulate, maloʻo, a laila 14 mesh screen whole grain, me ka vector magnesium stearate, me 100mm circular belt word (PPA0.25) stamping tablets. Me ka starch ma ke ʻano he disintegrating agent, ʻaʻole emi ka nui o ka hoʻoheheʻe ʻana o kēia papa ma mua o 80%/2min, ʻoi aku ka kiʻekiʻe ma mua o nā huahana like ma Iapana.
4.5 Hoʻoheheʻe hana HPMC-4000, HPMC-4500 a i ʻole HPMC-5000 0.3g, sodium chloride 0.45g, potassium chloride 0.37g, borax 0.19g, 10% ammonium chlorbenzylammonium solution 0.02ml, wai i hoʻohui ʻia i 100ml. ʻO kāna ʻano hana ʻana, ʻo ia ka HPMC i hoʻokomo ʻia i loko o ka wai 15ml, ma 80 ~ 90 ℃ wai piha e lawe i kahi, e hoʻohui i 35ml wai, a laila e hoʻokomo i nā ʻāpana i koe o ka wai wai 40ml i hui like ʻia, e hoʻohui i ka wai i ka nui piha, a laila e hui like ʻia, e kū i ka pō, e ninini mālie i ka kānana, e kānana i loko o ka pahu i hoʻopaʻa ʻia, e sterilized ma 98 ~ 100 ℃ no 30min, ʻo ia hoʻi, ʻO ka pH mai 8.4 ° C a i 8.6 ° C. HOʻOHANA ʻIA KĒIA HUAHANA NO KA NEʻE ʻANA O KA HAEHAE, HE PANI MAIKAʻI NO KA HAEHAE, I KA WĀ E HOʻOHANA ʻIA AI NO KA microscopy keʻena ANTERIOR, hiki ke hoʻonui kūpono ʻia ka nui o kēia huahana, 0.7% ~ 1.5% ka mea kūpono.
4.6 Nā papa hoʻokuʻu i kāohi ʻia ʻo Meththorphan paʻakai resin meththorphan 187.5mg, lactose 40.0mg, PVP70.0mg, vapor silica 10mg, 40.0 mGHPMC-603, 40.0mg ~ microcrystalline cellulose phthalate-102 a me ka magnesium stearate 2.5mg. Hoʻomākaukau ʻia ia ma ke ʻano he papa ma ke ʻano maʻamau. Hoʻohana ʻia kēia huahana ma ke ʻano he mea hoʻokuʻu i kāohi ʻia.
4.7 No nā papa avantomycin ⅳ, ua hoʻoulu ʻia, kāwili ʻia, hoʻopili ʻia, a hoʻomaloʻo ʻia he 2149g avantomycin ⅳ monohydrate a me 1000ml hui wai isopropyl o 15% (hui nui) eudragitL-100 (9:1). Ua kāwili maikaʻi ʻia nā granules maloʻo 575g a me 62.5g hydroxypropylocellulose E-50, a laila ua hoʻohui ʻia he 7.5g stearic acid a me 3.25g magnesium stearate i nā papa e loaʻa ai ka hoʻokuʻu mau ʻana o nā papa vanguard mycin ⅳ. Hoʻohana ʻia kēia huahana ma ke ʻano he mea hoʻokuʻu lohi.
4.8 Nā granules hoʻokuʻu mau ʻia ʻo Nifedipine Ua hui pū ʻia he 1 ʻāpana nifedipine, 3 ʻāpana hydroxypropyl methyl cellulose a me 3 ʻāpana ethyl cellulose me ka mea hoʻoheheʻe i hui ʻia (ethanol: methylene chloride = 1:1), a ua hoʻohui ʻia he 8 ʻāpana palaoa kulina e hana i nā granules ma o ke ʻano hana hoʻoheheʻe waena. ʻAʻole i hoʻopilikia ʻia ka helu hoʻokuʻu lāʻau lapaʻau o nā granules e ka loli o ka pH kaiapuni a ua lohi ma mua o nā granules i loaʻa ma ke kālepa. Ma hope o 12 mau hola o ka lawelawe waha, ʻo ka nui o ke koko kanaka he 12mg/ml, a ʻaʻohe ʻokoʻa pākahi.
4.9 ʻO ka Propranhaol hydrochloride sustained release capsule Propranhaol hydrochloride 60kg, microcrystalline cellulose 40kg, e hoʻohui ana i 50L wai e hana i nā granules. Ua hui pū ʻia ʻo HPMC1kg a me EC 9kg i loko o ka solvent i hui ʻia (methylene chloride: methanol =1:1) 200L e hana i ka hopena uhi, me ka nui o ke kahe o 750ml/min e pīpī ana ma luna o nā ʻāpana poepoe ʻōwili, nā ʻāpana i uhi ʻia ma o ka nui o ka pore o 1.4mm screen all particles, a laila hoʻopiha ʻia i loko o ka capsule pōhaku me ka mīkini hoʻopiha capsule maʻamau. Loaʻa i kēlā me kēia capsule he 160mg o nā ʻāpana poepoe propranolol hydrochloride.
4.10 Ua hoʻomākaukau ʻia nā papa iwi Naprolol HCL ma ke kāwili ʻana i ka naprolol HCL :HPMC: CMC-NA ma ka lakio o 1:0.25:2.25. Ua kokoke ka helu hoʻokuʻu lāʻau i ka ʻole o ke kauoha i loko o 12 mau hola.
Hiki ke hana ʻia nā lāʻau ʻē aʻe me nā mea iwi i hui pū ʻia, e like me metoprolol: HPMC: CMC-NA e like me: 1:1.25:1.25; Allylprolol:HPMC e like me ka lakio 1:2.8:2.92. Ua kokoke ka helu hoʻokuʻu lāʻau i ka ʻole o ke kauoha i loko o 12 mau hola.
4.11 Ua hoʻomākaukau ʻia nā papa iwi o nā mea i hui ʻia o nā derivatives ethylaminosine ma ke ʻano maʻamau e hoʻohana ana i ka hui ʻana o ka micro powder silica gel: CMC-NA:HPMC 1:0.7:4.4. Hiki ke hoʻokuʻu ʻia ka lāʻau no 12h ma vitro a ma vivo, a he pilina maikaʻi ko ke ʻano hoʻokuʻu linear. Ua wānana nā hopena o ka hoʻāʻo paʻa wikiwiki e like me nā lula FDA e hiki i ke ola mālama o kēia huahana a hiki i 2 mau makahiki.
4.12 Ua hoʻoheheʻe ʻia ʻo HPMC (50mPa·s) (5 ʻāpana), HPMC (4000 mPa·s) (3 ʻāpana) a me HPC1 i loko o 1000 ʻāpana wai, ua hoʻohui ʻia he 60 ʻāpana acetaminophen a me 6 ʻāpana silica gel, ua hoʻoulu ʻia me kahi homogenizer, a ua pīpī maloʻo. Loaʻa i kēia huahana he 80% o ka lāʻau lapaʻau nui.
4.13 Ua helu ʻia nā papa iwi gel hydrophilic Theophylline e like me ke kaumaha o ka papa holoʻokoʻa, 18%-35% theophylline, 7.5%-22.5% HPMC, 0.5% lactose, a me kahi nui kūpono o ka lubricant hydrophobic i hoʻomākaukau maʻamau ʻia i loko o nā papa hoʻokuʻu i kāohi ʻia, hiki ke mālama i ka nui o ke koko o ke kino kanaka no 12h ma hope o ka lawelawe waha.
Ka manawa hoʻouna: Sep-20-2022