Box-Behnkenov eksperimentalni dizajn u izradi pektin-kompritol ATO 888 obloženih tableta za ciljanu isporuku mesalamina u kolon

The aim of this study was to investigate the combined influence of 3 independent variables in the compression coated tablet of mesalamine for ulcerative colitis. A 3-factor, 3-level Box-Behnken design was used to derive a second order polynomial equation and construct contour plots to predict responses. The independent variables selected were: percentage of polymers (pectin and compritol ATO 888) in compression coating (X1), coating mass (X2) and coating force (X3). Fifteen batches were prepared and evaluated for percent of drug released in 5 h (Y5), time required for 50 % mesalamine to disolve (t50) with rat cecal (RC) content and without rat cecal content (t50), percent of drug released in 24 h in the presence of rat cecal content (Y24 with RC). Transformed values of independent and dependent variables were subjected to multiple regressions to establish a full-model second-order polynomial equation. F was calculated to confirm the omission of insignificant terms from the full-model equation. The computer optimization process and contour plots predicted the levels of independent variables X1, X2, and X3 (0, 0.2 and –0.15 respectively) for colon targeting and total percent of drug released up to 24 h.Cilj rada bio je ispitati utjecaj tri nezavisne varijable u obloženim tabletama mesalamina za ulcerativni kolitis. 3-faktorijalni, Box-Behnkenov dizajn na 3 nivoa upotrijebljen je za dobivanje polinomske jednadžbe drugog reda i konstruiranje konturnih krivulja za predviđanje odgovora. Izabrane nezavisne varijable bile su: udio polimera (pektin i kompritol ATO 888) u oblaganju kompresijom (X1), masa tvari za oblaganje (X2) i sila za oblaganje (X3). Izrađeno je petnaest pripravaka kojima su ispitani sljedeći parametri: udio lijeka oslobođenog nakon 5 h (Y5), vrijeme potrebno za otapanje 50 % mesalamina (t50) uz i bez prisutnosti crijevnog sadržaja štakora (RC), postotak oslobođenog lijeka tijekom 24 h u prisutnosti crijevnog sadržaja (Y24 uz RC). Transformirane vrijednosti nezavisnih i zavisnih varijabla podvrgnute su višestrukoj regresijskoj analizi da se odredi polinomska jednadžba drugog reda potpunog modela. F vrijednost izračunata je da se potvrdi izostavljanje neznačajnih članova iz jednadžbe potpunog modela. Kompjutorski optimizirani proces i krivulje predviđaju nezavisne varijable X1, X2 i X3 (0, 0,2, odnosno –0,15) za ciljanu isporuku u kolon i ukupni postotak lijeka oslobođenog tijekom 24 h

ENHANCEMENT OF DISSOLUTION RATE OF MODAFINIL USING SOLID DISPERSIONS WITH POLYETHYLENEGLYCOLS

Solid  dispersions  (SDs)  of  modafinil  (MDF)  were  prepared using polyethyleneglycols (PEGs), in 1;1, 1;2 and 1;4 proportions by  fusion,  solvent  evaporation  and  physical  mixing  method. Differential  scanning  calorimetry  (DSC)  and  X-ray  powder diffractometry (XRD)  were  used to examine the physical state  of the  drug.  The  data  from  the  XRD  showed  that  the  drug  was converted  to  amorphous  form  as  the  number  and  intensity  of peaks  were  decreased  in  solid  dispersion  as  compared  to  pure drug and physical mixture of drug and carrier. DSC thermograms also  confirmed  the  change  in  physical  state  of  the  drug  as  the peaks were altered or disappeared. With the  highest  ratio of the carriers (1:4), the drug  solubility was enhanced by 38.68, 34.78 and 9.29 folds in solvent evaporation, fusion and physical mixing methods  respectively.  Solid  dispersion  batch  S6  containing drug:PEG6000  in  1:4,  was  selected  to  be  formulated  as  tablet (batch  TS6)  and  evaluated  for in  vitro drug  dissolution  &  six month  stability.  An  increased  dissolution  rate  of  modafinil  was observed  from  SDs  and  PMs,  as  compared  to  pure  crystalline drug.  The  dissolution  rate  of  modafinil  from  its  PMs  or  SDs increased with an increasing amount of polymer.Key  words:  Fusion,  solvent  evaporation,  physical  mixture,  in  vitro dissolution, characterization.

Intranasal mucoadhesivemicroemulsion for neuroprotective effect of curcuminin mptp induced Parkinson model

This study was to investigate the neuroprotective effect of curcumin against inflammation-mediated dopaminergic neurodegeneration in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mice model of Parkinson's disease (PD). Curcumin loaded sodium hyaluronate based mucoadhesive microemulsion (CMME) was developed by using Box Behnken design of Response surface method (RSM) and was characterized. Male C57BL/6 mice were first treated with four intraperitoneal injections of MPTP (20 mg/kg of body weight) at 2 h intervals followed CMME intranasal administration for 14 days at 2.86 mg of curcumin/kg of body weight per once a day. Optimal CMME containing 3% Capmul MCM as oil phase, 37 % of Accenon CC and Transcutol HP at 2.5:1 ratio and 0.5% sodium hyaluronate was stable, non-ciliotoxic with 57.66 nm±3.46 as average globule size. PdI value (0.190 ± 0.19) and TEM result depicted the narrow size distribution of CMME.All three independent variables had a significant effect (

Priprava i in vitro karakterizacija mikrosfera amoksicilina dobivenih metodom sušenja sprejom

The purpose of the present study was to design mucoadhesive chitosan microspheres containing amoxycillin. Chitosan microspheres with a small particle size and good sphericity were prepared by a spray-drying method followed by chemical treatment with a chemical crosslinking agent (glutaraldehyde). Parameters affecting the extent of crosslinking were the crosslinking time and the concentration of the crosslinker agent. Crosslinked spray-dried chitosan microspheres were analyzed for their morphological aspects, particle size, drug entrapment efficiency, swelling percent and in vitro drug release. Batch M4 with a drug polymer ratio of 1:2, dissolved in minimum concentration of acetic acid solution treated with glutraldehyde, was found to be optimal giving controlled drug release for 10 h. It was found that both the increase of glutaraldehyde concentration and crosslinking duration decreased the swelling capacity of chitosan microspheres. This could be directly correlated to drug release from the microspheres.Cilj ovog rada bio je priprava mukoadhezivnih kitozanskih mikrosfera amoksicilina. Mikrosfere male veličine čestica i dobre sferičnosti pripravljene su metodom sušenja sprejom, te obradom s glutaraldehidom kao sredstvom za umrežavanje. Stupanj umrežavanja ovisio je o vremenu umrežavanja i koncentraciji sredstva za umrežavanje. Umreženim kitozanskim mikrosferama određen je oblik, veličina čestica, količina uklopljenog lijeka, postotak bubrenja i in vitro oslobađanje ljekovite tvari. Pripravak M4 s optimalnim svojstvima i kontroliranim oslobađanjem amoksicilina tijekom 10 sati pripravljen je pomoću smjese polimera omjera 1:2 otopljenih u razrijeđenoj octenoj kiselini, te umreženih pomoću glutraldehida. Povećanje koncentracije glutaraldehida i trajanja umrežavanja smanjuje sposobnost bubrenja kitozanskih mikrosfera, što je u izravnoj korelaciji s oslobađanjem lijeka iz mikročestica

Razvoj i vrednovanje novog ljekovitog pripravka hidroklortiazida za kontrolirano oslobađanje u želucu in situ

In situ forming intragastric controlled-release formulation is a new technology in the field of oral controlled release delivery systems. The objective of this study was to develop the formulations that can control drug release up to 24 hours. In addition, a combination of appropriate polymers and solvents was selected that could form a drug loaded gel at the process temperature of 60–70 °C, which could turn into a rigid mass upon exposure to dissolution fluid at body temperature. The drug release mechanism from this rigid mass was controlled by different formulation factors such as different polymer grades, polymer concentrations, hydrophobicity or hydrophilicity of solvents, different drug loadings, and physicochemical properties of additional excipients. After evaluating different formulation factors, Ethocel 10 FP and triethyl citrate were selected for further studies using hydrochlorothiazide as a model drug. Polynomial correlation between viscosity of the blank gel and drug release profile was also obtained.In situ izrada pripravka za kontrolirano oslobađanje nova je tehnologija u području peroralnih sustava za kontrolirano oslobađanje ljekovite tvari. Cilj rada bio je razvoj pripravka za kontrolirano oslobađanje lijeka do 24 sata. Provedena su preliminarna ispitivanja fizikalne kompatibilnosti različitih otapala s tvrdom želatinskom kapsulom. Ispitane su različite kombinacije polimera i otapala kako bi se pronašle kombinacije koje mogu tvoriti gel s uklopljenom ljekovitom tvari pri temperaturi izrade od 60–70 °C koji prelazi u čvrstu strukturu nakon izlaganja tekućem mediju za oslobađanje pri tjelesnoj temperaturi. Mehanizam oslobađanja lijeka iz te čvrste strukture kontroliraju različiti faktori poput stupnja polimerizacije, koncentracije polimera, hidrofobnosti ili hidrofilnosti otapala, količine uklopljenog lijeka i fizičko-kemijskih svojstava dodanih pomoćnih tvari. Nakon evaluacije različitih formulacijskih faktora, za daljnja ispitivanja odabrani su Ethocel 10 FP i trietil-citrat. Kao model-lijek upotrijebljen je hidroklortiazid. Utvrđena je polinomska korelacija s viskoznošću gela bez ljekovite tvari. Određen je profil oslobađanja lijeka

Design and evaluation of famotidine mucoadhesive nanoparticles for aspirin induced ulcer treatment

The present study was performed to design and evaluate the famotidine loaded mucoadhesive nanosuspension for aspirin induced ulcer. A 3-factor, 3-level Box-Behnken design was applied to study the effects of amount of the beads (X1), PVPK-30(X2) and Tween-80 (X3) on the particle size (Y1), and cumulative percentage drug released after 1h (Y2). The optimization was performed using the desirability function and contour plots. The scanning electron microscopy (SEM) showed the nanoparticles as spherical in shape. The differential scanning calorimetry (DSC) analysis indicated that there was substantial crystallinity change in the nanoparticle compared with the pure drug. Ex-vivo mucoadhesion study showed that famotidine mucoadhesive nanoparticles possessed higher mucoadhesion than the famotidine nanoparticles. The in vivo studies on aspirin-induced rats indicated the lowering in ulcer index for famotidine mucoadhesive nanoparticles was 0.46+0.011, which was significantly better than the effect of traditional famotidine suspension (0.66+0.035). Famotidine mucoadhesive nanosuspension could be prepared using the media milling technique and allowing significant reduction in ulcer index compared to famotidine suspension