The modern drug alaptide, synthetic dipeptide, shows regenerative effects and effects on the epitelisation process. A commercial product consisting of 1% alaptide hydrophilic cream is authorised for use in veterinary practice. This study focuses on the formulation of alaptide into semi-synthetic polymer-based hydrogels. The aim of the present study is to prepare hydrogels and to evaluate the liberation of alaptide from hydrogels. The hydrogels were prepared on the basis of three gel-producing substances: methylcellulose, hydroxyethylcellulose and hydroxypropylcellulose. To enhance the drug release from hydrogel humectants, glycerol, propylene glycol and ethanol in various concentrations were evaluated. The permeation of the alaptide from gels into the acceptor solution was evaluated with the use of the permeable membrane neprophane. The amount of drug released from prepared hydrogels was determined spectrophotometrically. Hydrogels with optimal alaptide liberation properties were subjected to the study of rheological properties in the next phase. The optimal composition of hydrogel as established in this study was 1% alaptide + 3% hydroxyethylcellulose with the addition of 10% glycerol as humectant. Due to the advantageous properties of hydrogels in wounds, alaptide could be incorporated into a hydrogel base for use in veterinary medicine.
- Klíčová slova
- alaptid, zvlhčovadla,
- MeSH
- celulosa chemie MeSH
- cyklické peptidy * farmakokinetika MeSH
- dermatologické látky klasifikace MeSH
- epitel účinky léků MeSH
- farmaceutické pomocné látky * MeSH
- hojení ran účinky léků MeSH
- hormon inhibující uvolňování MSH MeSH
- hydrogely * chemie terapeutické užití MeSH
- neuropeptidy MeSH
- uvolňování léčiv MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
Predmetom príspevku je hodnotenie liberácie liečiva alaptid z gélov a jeho permeácia cez rôzne typy permeačných membrán. Pripravili sa gély na báze troch rôznych polymérov (3 % chitosan; 2,5 % hydroxypropylcelulóza; 3 % hydroxyetylcelulóza) v rôznej koncentrácii s prísadou humaktantov (5 %; 15 % propylénglykol a 0 % glycerol) a konzervantu 0,3 % Sepicide HBR a liečiva 1 % alaptid a gély bez liečiva. Prestup liečiva z gélov do akceptorového roztoku sa hodnotil cez nasledovné membrány: celofán, kuracia koža, zvlečená hadia koža a stena tenkého čreva. Z výsledkov merania bolo zistené najväčšie percento uvoľneného alaptidu cez stenu tenkého čreva, menej cez kuraciu kožu a najmenej sa uvoľnilo cez hadiu kožu. V práci sa hodnotili aj reologické vlastnosti pripravených hydrogélov. Pseudoplastický tok bol zistený iba v prípade hydrogélu na báze hydroxypropylcelulózy. Naopak to bolo pri hydrogéloch na báze chitosanu a hydroxyetylcelulózy, ktoré vykazovali výrazný tixotropný charakter a miera tixotropie sa s časom zväčšovala. Na základe výsledkov merania pH boli vzorky na báze chitosanu a hydroxypropylcelulózy vyhodnotené ako nevyhovujúce, nakoľko dosahovali nižšie hodnoty pH a mohli by spôsobiť podráždenie pokožky. Fyziologickým hodnotám pH kože zodpovedal hydrogél na báze hydroxyetylcelulózy a to i po 14. dňoch po príprave.
The paper evaluates the liberation of alaptide from gels through various types of permeable membranes. The gels were prepared on the basis of three different polymers (3% chitosan; 2.5% hydroxypropyl cellulose; 3% hydroxyethyl cellulose) in different concentrations with additions of humectants (5 %; 15% propylene glycol and 10% glycerol) and the preserving agent, 0.3% Sepicide HBR with 1% alaptide, and finally without the drug. The permeation of the drug from gels into the acceptor solution was evaluated with the use of the following membranes: the hydrophilic membrane from Chemosvit, the chicken skin, the stripped snakeskin, and the wall of the small intestine. The measurements showed that the highest percentage of the drug penetrated through the small intestine, a smaller percentage through the chicken skin, and the smallest amount through the snakeskin. Rheological properties of the prepared hydrogels were evaluated as well. The pseudo-plastic flow was only confirmed for the hydrogel prepared on the basis of hydroxypropyl cellulose. An utterly opposite situation was with the hydrogels prepared on the basis of chitosan and hydroxyethyl cellulose. They showed a significant thixotropic character and the degree of thixotropy increased with time. Based on the results of the pH measurement, the samples prepared on the basis of chitosan and hydroxypropyl cellulose have been shown to be inconvenient because they reached a lower pH and had a potential of causing skin irritation. The hydroxyethyl cellulose hydrogel matched the physiological values of skin pH even after 14 days since its preparation.
Príspevok sa zaoberá výberom optimálnych pomocných látok zo skupiny enhancerov a humektantov pri formulácii chlórhexidínu do liekovej formy – chitosanového hydrogélu. Koncentrácia liečiva je vždy konštantná – 0,1% (m/m) a gélotvornej látky 2,5% (m/m). Liečivo chlórhexidín je jedno z najpoužívanejších antiseptík pri zápaloch ústnej dutiny. V práci sa hodnotilo jeho uvoľňovanie z hydrogélov bez a v prítomnosti Polysorbátu 80 v 0,1 a 0,5% (m/m) a glycerolu v 10% (m/m). Obsah liečiva sa stanovil spektrofotometricky a zistilo sa, že optimálne zloženie hydrogélu je: 0,1% chlórhexidín + 2,5% chitosan + 0,1% Polysorbát 80, kde sa uvoľnilo najviac liečiva a tento hydrogél vykazoval tixotropné vlastnosti, ktoré sú z hľadiska aplikácie žiaduce.
The paper deals with the selection of optimal auxiliary substances from the group of enhancers and humectants for the formulation of chlorhexidin into the dosage form chitosan hydrogel. The concentrations of the active ingredient and the gel-producing substance are always constant, 0.1% (m/m) and 2.5% (m/m), respectively. The active ingredient chlorhexidin is one of the most widely used antiseptic agents to treat the inflammations of the oral cavity. The paper evaluated its release from hydrogels without and with Polysorbat 80 in 0.1 and 0.5% (m/m) and glycerol in 10% (m/m). The content of the active ingredients was determined spectrophotometrically, the optimal composition of hydrogel being: 0.1% chlorhexidin + 2.5% chitosan + 0.1% Polysorbat 80, where the largest amount of the active ingredient was released and this hydrogel showed thixotropic properties desirable from the standpoint of administration.
Príspevok sa zaoberá skúmaním vplyvu bežne používaných humektantov glycerolu (GL) a propylénglykolu (PG) na liberáciu alaptidu (ALA) z 3% (m/m) chitosanových (CHIT) hydrogélov v porovnaní s liberáciou alaptidu (ALA) z krému. Obsah GL a PG v jednotlivých hydrogéloch bol 5 %, 10 %, 15 % (m/m). Alaptid je regeneračne pôsobiaci syntetický derivát prolyl-leucyl-glycin amidu, zatiaľ používaný vo veterinárnej medicíne. Jeho obsah v skúmaných hydrogéloch a kréme bol 1 % (m/m). Experimenty boli vykonané in vitro v temperovanej permeačnej aparatúre. Množstvo uvoľneného ALA bolo merané spektrofotometricky pri 212 nm, po 14. dňoch od prípravy jednotlivých chitosanových hydrogélov a krému. ALA sa uvoľnil v nasledovných množstvách: 14,06 % sa uvoľnilo z krému; 36,54 % z hydrogélu s obsahom 5 % GL (m/m); 37,85 % z hydrogélu s 5 % PG (m/m); 38,37 % z hydrogélu bez obsahu GL a PG; 40,71 % z hydrogélu s obsahom 15 % GL (m/m); 41,21 % z hydrogélu s 10 % GL (m/m); 42,72 % ALA sa uvoľnilo z hydrogélu s 10 % PG (m/m); 43,78 % z hydrogélu s 15 % PG (m/m). V závere možno usúdiť, že prítomnosť GL a PG malo vplyv na liberáciu ALA z dermálnych polotuhých liekov.
The paper examines the effects of routinely used humectants of glycerol (GL) and propylene glycol (PG) on the liberation of alaptid (ALA) from 3% (m/m) chitosan (CHIT) hydrogels in comparison with the liberation of alaptid (ALA) from cream. The contents of GL and PG in the individual hydrogels were 5%, 10%, 15% (m/m). Alaptid is a regeneratively acting synthetic derivative of prolyl-leucyl-glycin amide, which is for the time being used in veterinary medicine. Its content in the hydrogels and cream under study was 1% (m/m). The experiments were performed in vitro in a tempered permeating apparatus. The amount of the released ALA was measured spectrophotometrically at 212nm, 14 day after the preparation of the individual chitosan hydrogels and cream. ALA was liberated in the following amounts: 14.06% was released from cream; 36.54% from hydrogel containing 5% GL (m/m); 37.85% from hydrogel with 5% PG (m/m); 38.37% from hydrogel not containing GL and PG; 40.71% from hydrogel containing 15% GL (m/m); 41.21% from hydrogel with 10% GL (m/m); 42.72% ALA was released from hydrogel with 10% PG (m/m); 43.78% from hydrogel with 15% PG (m/m). It can be concluded that the presence of GL and PG exerted effects on liberation of ALA from dermal semisolid preparations.
