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

OPTIMIZATION AND CHARACTERIZATION OF DOXORUBICIN LOADED SOLID LIPID NANOSUSPENSION FOR NOSE TO BRAIN DELIVERY USING DESIGN EXPERT SOFTWARE

Objective: The goal of the current study was to investigate the possible use of solid lipid nanosuspension (SLNs) as a drug delivery method to boost doxorubicin (DOX) brain-targeting performance after intranasal (i. n.) administration.  Methods: 33 factorial design was applied for optimization by using lipid concentration, surfactant concentration, and High-speed homogenizer (HSH) stirring time as dependent variables, and their effect was observed on particles size, Polydispersity index (PDI), and entrapment efficiency.  Results: With the composition of Compritol® 888 ATO (4.6 % w/v), tween 80 (1.9 % w/v), and HSH stirring time, the optimized formula DOX-SLNs prepared (10 min). Particle size, PDI, zeta potential, entrapment efficiency, percent in vitro release were found to be 167.47±6.09 nm, 0.23±0.02, 24.1 mV, 75.3±2.79, and 89.35±3.27 percent in 24 h, respectively, for optimized formulation (V-O). No major changes in particle size, zeta potential, and entrapping efficiency were found in the stability studies at 4±2 °C (refrigerator) and 25±2 °C/60±5% RH up to 3 mo.  Conclusion: Following the non-invasive nose-to-brain drug delivery, which is a promising therapeutic strategy, the positive findings confirmed the current optimized DOX-loaded SLNs formulation

EFFECT OF HPMC/CARBOPOL ON THE RELEASE OF CHLORPHENIRAMINE MALEATE FROM MATRIX TABLETS

Chlorpheniramine maleate is widely used in treatment for allergic disorder and cold. The controlled release matrix tablets of chlorpheniramine maleate were prepared using HPMC K15M, HPMC K100M and carbopol and studied their effect on drug release. Prepared tablets were evaluated for various physical parameters. In vitro drug release study shows that slow release in HPMC K100M than other two polymers. If concentration of polymer increases than the drug release is decreases due to formation of polymeric matrix. Zero order, first order, Higuchi’s and Korsmeyer’s equations applied to know the mechanism of drug release from prepared tablets. The similarity and dissimilarity factor found to be 77.88 and 4.14, respectively for drug release in stability study which shows there was no significant difference in drug release.Key words: Chlorpheniramine maleate, matrix tablet, HPMC K15M, HPMC K100M, carbopol and swelling inde

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