Kalulu coccidiosis ndi matenda omwe amapezeka paliponse omwe amayamba chifukwa cha mtundu umodzi kapena zingapo mwa mitundu 16 ya apicomplexan genus.Eimeria stiedae.^1-4Zizindikiro zodziwika bwino za matendawa zimadziwika ndi kufooka, kuchepa kwa chakudya, kutsekula m'mimba kapena kudzimbidwa, kukulitsa kwa chiwindi, ascites, icterus, kutsekula m'mimba, ndi kufa.³Chiphuphu cha akalulu chimatha kupewedwa ndikuchizidwa pogwiritsa ntchito mankhwala.^1,3,5,6Toltrazuril (Tol), 1- [3-methyl-4- (4-trifluoromethylsulfanyl-phenoxy)-phenyl]-3-methyl-1,3,5-triazin-2,4,6-trione (Chithunzi 1), ndi symmetrical triazinetrione pawiri yomwe imagwiritsidwa ntchito kwambiri popewa komanso kuthana ndi coccidiosis.^7-10Komabe, chifukwa cha kusungunuka kwamadzi kwamadzi, Tol ndizovuta kutengeka ndi thirakiti la m'mimba (GI). Zotsatira zachipatala za Tol zachepetsedwa chifukwa cha kusungunuka kwake mu thirakiti la GI.

Chithunzi 1 Kapangidwe ka mankhwala a toltrazuril.

Kusungunuka kosauka kwamadzi kwa Tol kwagonjetsedwa ndi njira zina, monga kufalikira kolimba, mphamvu ya ultrafine, ndi nanoemulsion.^11-13Monga njira zothandiza kwambiri pakuwonjezera kusungunuka, Tol solid dispersion idangowonjezera kusungunuka kwa Tol mpaka nthawi 2,000,¹¹zomwe zimasonyeza kuti kusungunuka kwake kumafunikabe kuwonjezeredwa kwambiri kudzera mu njira zina. Kuphatikiza apo, kubalalitsidwa kolimba ndi nanoemulsion ndizosakhazikika komanso zovuta kusungirako, pomwe mphamvu ya ultrafine imafunikira zida zapamwamba kuti apange.

β-cyclodextrin (β-CD) imagwiritsidwa ntchito ponseponse chifukwa cha kukula kwake kwapadera, mphamvu ya mankhwala osokoneza bongo, komanso zowonjezereka za kukhazikika kwa mankhwala, kusungunuka, ndi bioavailability.^14,15Pakuwongolera kwake, β-CD yalembedwa m'magwero ambiri a pharmacopoeia, kuphatikiza US Pharmacopoeia/National Formulary, European Pharmacopoeia, ndi Japan Pharmaceutical Codex.^16,17Hydroxypropyl–β-CD (HP-β-CD) ndi hydroxyalkyl β-CD yochokera ku hydroxyalkyl β-CD yomwe imaphunziridwa mozama mu mankhwala ophatikiza mankhwala chifukwa cha mphamvu zake zophatikizira komanso kusungunuka kwamadzi kwambiri.^18-21Kafukufuku wa Toxicologic adanenanso za chitetezo cha HP-β-CD mumayendedwe am'mitsempha ndi pakamwa kwa thupi la munthu,²²ndi HP-β-CD akhala akugwiritsidwa ntchito m'mapangidwe achipatala kuti athetse vuto losungunuka bwino komanso kupititsa patsogolo bioavailability.²³

Sikuti mankhwala onse ali ndi zinthu zomwe ziyenera kupangidwa kukhala zovuta ndi HP-β-CD. Tol adapezeka kuti ali ndi katunduyo potengera kuchuluka kwa kafukufuku wowunika. Kuonjezera kusungunuka ndi bioavailability wa Tol mwa kuphatikiza mapangidwe ovuta ndi HP-β-CD, toltrazuril-hydroxypropyl-β-cyclodextrin inclusion complex (Tol-HP-β-CD) inakonzedwa ndi njira yothetsera vutoli mu phunziro ili, ndi yopyapyala. -layer chromatography (TLC), Fourier transform infrared (FTIR) spectroscopy, ndi nuclear magnetic resonance (NMR) spectroscopy anagwiritsidwa ntchito kusonyeza Tol-HP-β-CD anapeza. Mbiri ya pharmacokinetic ya Tol ndi Tol-HP-β-CD mu akalulu pambuyo poyang'anira pakamwa amafananizidwanso mu vivo.