I-Rabbit coccidiosis yisifo esitholakala yonke indawo esibangelwa uhlobo olulodwa noma ngaphezulu kweziyi-16 zohlobo lwe-apicomplexan.I-Eimeria stiedae.^1-4Izimpawu zomtholampilo ezijwayelekile zalesi sifo zibonakala ngokuba buthuntu, ukunciphisa ukusetshenziswa kokudla, isifo sohudo noma ukuqunjelwa, ukwanda kwesibindi, ama-ascites, i-icterus, ukuqunjelwa kwesisu, nokufa.³I-Coccidiosis konogwaja ingavinjelwa futhi ilashwe ngokusebenzisa izidakamizwa.^1,3,5,6I-Toltrazuril (i-Tol), i-1--[3-methyl-4-(4-trifluoromethylsulfanyl-phenoxy)-phenyl]-3-methyl-1,3,5-triazin-2,4,6-trione (Umfanekiso 1), iyinhlanganisela ye-symmetrical triazinetrione esetshenziswa kabanzi ukuvimbela kanye nokulwa ne-coccidiosis.^7-10Kodwa-ke, ngenxa yokungancibiliki kahle kwamanzi, i-Tol inzima ukumuncwa i-gastrointestinal (GI) tract. Imiphumela yomtholampilo ye-Tol yehlisiwe ngenxa yokuncibilika kwayo epheshaneni le-GI.

Umfanekiso 1 Isakhiwo samakhemikhali se-toltrazuril.

Ukuncibilika okungalungile kwe-aqueous kwe-Tol kunqotshwe amasu athile, njengokuhlakazeka okuqinile, amandla e-ultrafine, ne-nanoemulsion.^11-13Njengamasu asebenzayo njengamanje okwandisa ukuncibilika, i-Tol solid dispersion yandise ukuncibilika kwe-Tol kuya ezikhathini ezingu-2,000,¹¹okubonisa ukuthi ukunyibilika kwayo kusadinga ukuthuthukiswa kakhulu ngezinye izindlela. Ngaphezu kwalokho, ukuhlakazeka okuqinile kanye ne-nanoemulsion azinzile futhi akulula ukuyigcina, kuyilapho amandla e-ultrafine edinga imishini eyinkimbinkimbi ukuze akhiqize.

I-β-cyclodextrin (β-CD) isetshenziswa kabanzi ngenxa yobukhulu bayo bomgodi obuhlukile, ukusebenza kahle kokuhlanganiswa kwezidakamizwa, kanye nezithuthukisi zokuzinza kwezidakamizwa, ukunyibilika, kanye ne-bioavailability.^14,15Ngesimo sayo sokulawula, i-β-CD isohlwini lwemithombo eminingi ye-pharmacopoeia, okuhlanganisa i-US Pharmacopoeia/National Formulary, i-European Pharmacopoeia, kanye ne-Japanese Pharmaceutical Codex.^16,17I-Hydroxypropyl–β-CD (HP-β-CD) iphuma ku-hydroxyalkyl β-CD ecutshungulwa kabanzi ekufakweni kwezidakamizwa ngenxa yekhono layo lokufakwa kanye nokuncibilika kwamanzi okuphezulu.^18-21Ucwaningo lwe-Toxicologic lubike ngokuphepha kwe-HP-β-CD ekuphathweni kwe-intravenous kanye nomlomo emzimbeni womuntu,²²kanye ne-HP-β-CD isetshenziswe ekwakhiweni komtholampilo ukuze kunqotshwe izinkinga zokungancibiliki kahle kanye nokuthuthukisa i-bioavailability.²³

Akuyona yonke imithi enezakhiwo okufanele zenziwe zibe yinkimbinkimbi nge-HP-β-CD. U-Tol watholakala enezakhiwo ezisekelwe enanini elikhulu lomsebenzi wocwaningo lokuhlola. Ukwandisa i-solubility kanye ne-bioavailability ye-Tol ngokufaka ukwakheka okuyinkimbinkimbi nge-HP-β-CD, i-toltrazuril-hydroxypropyl-β-cyclodextrin inclusion complex (i-Tol-HP-β-CD) yalungiswa ngendlela yokuvuselela isisombululo kulolu cwaningo, futhi mncane. -i-layer chromatography (TLC), i-Fourier transform infrared (FTIR) spectroscopy, kanye ne-nuclear magnetic resonance (NMR) i-spectroscopy yasetshenziswa ukuze kubonakale i-Tol-HP-β-CD etholiwe. Amaphrofayili e-pharmacokinetic we-Tol ne-Tol-HP-β-CD konogwaja ngemva kokuphathwa ngomlomo aphinde aqhathaniswa ne-vivo.