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

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

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.

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

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 evaluacija mukoadhezivnih filmova glipizida

Glipizide is mainly absorbed in the proximal areas of the gastrointestinal tract. The purpose of this study was formulation and evaluation of mucoadhesive films to prolong the stay of drug in its absorption area. Glipizide was formulated in a mucoadhesive film that could be retained in the stomach for prolonged time intervals. Polymeric films were designed with various compositions of hydroxypropyl cellulose and polyethylene glycol 400 (PEG 400). Properties of the mucoadhesive film such as tensile strength, percentage elongation, swelling index, moisture content, pH and viscosity of polymeric dispersion, film thickness, drug concentration, uniformity and mucoadhesion in a simulated gastric environment were evaluated. In addition, percentage drug retained in stomach mucosa was estimated using a simulated dynamic stomach system as a function of time. Increase in hydroxypropyl cellulose concentration resulted in a higher tensile strength and elongation at break, while increase in concentration of PEG 400 was reflected in a decrease of tensile strength and increase of elongation at break. Glipizide/hydroxypropyl cellulose/PEG 400 (2.5:1:0.5) (GF5) was found to be the optimal composition for a novel mucoadhesive stomach formulation that showed good peelability, relatively high swelling index, moderate tensile strength, and stayed on rat stomach mucosa up to 8 h. In vivo testing of the mucoadhesive films with glipizide demonstrated a potential hypoglycemic effect.Glipizid se pretežno apsorbira u proksimalnom dijelu gastrointestinalnog trakta. Cilj rada je priprava i evaluacija mukoadhezivnih filmova s kojima bi se produljilo zadržavanje lijeka u predjelu apsorpcije. Pripravljeni su mukoadhezivni filmovi glipizida koji se produljeno zadržavaju u želucu. Polimerni filmovi sadržavali su različite količine hidroksipropil celuloze i polietilen glikola 400 (PEG 400). Evaluirana su sljedeća svojstva mukoadhezivnih filmova: čvrstoća, postotak elongacije, indeks bubrenja, sadržaj vlage, pH i viskoznost polimerne disperzije, debljina filma, koncentracija lijeka, jednolikost i mukoadhezivnost u simuliranom želučanom soku. Na dinamičkom modelu želuca određivan je i postotak lijeka koji se zadržava u sluznici želuca u ovisnosti o vremenu. Povećanjem koncentracije hidroksipropil celuloze povećavaju se čvrstoća i elongacija, dok se povećanje koncentracije PEG 400 reflektira na smanjenje čvrstoće i povećanje elongacije kod loma. Omjer glipizid/hidroksipropil celuloza/PEG 400 (2,5:1:0,5) (GF5) bio je optimalan za pripravu mukoadhezivnih formulacija, s dobrom kalavošću, relativno visokim indeksom bubrenja, umjerenom čvrstoćom te zadržavanjem u sluznici želuca štakora do 8 h. U in vivo testiranjima mukoadhesivni filmovi s glipizidom pokazali su potencijalni hipoglikemijski učinak

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

Stability-Indicating RP-HPLC Method for the Determination of Ambrisentan and Tadalafil in Pharmaceutical Dosage Form

A simple, rapid, and highly selective RP-HPLC method was developed for the simultaneous determination of Ambrisentan (AMB) and Tadalafil (TADA) drug substances in the fixed dosage strength of 10 mg and 40 mg, respectively. Effective chromatographic separation was achieved using a Hypersil GOLD C18 column (150 mm × 4.6 mm internal diameter, 5 μm particle size) with a mobile phase composed of methanol, water, and acetonitrile in the ratio of 40:40:20 (by volume). The mobile phase was pumped using a gradient HPLC system at a flow rate of 0.5 mL/min, and quantification of the analytes was based on measuring their peak areas at 260 nm. The retention times for Ambrisentan and Tadalafil were about 2.80 and 7.10 min, respectively. The reliability and analytical performance of the proposed HPLC procedure were statistically validated with respect to system suitability, linearity, ranges, precision, accuracy, specificity, robustness, detection, and quantification limits. Calibration curves were linear in the ranges of 1–20 μg/mL for Ambrisentan and 4–80 μg/mL for Tadalafil with correlation coefficients >0.990. The proposed method proved to be selective and stability-indicating by the resolution of the two analytes from the forced degradation (hydrolysis, oxidation, and photolysis) products. The validated HPLC method was successfully applied to the analysis of AMB and TADA in pharmaceutical dosage form

Validated Stability-Indicating RP-HPLC Method for the Simultaneous Determination of Azelnidipine and Olmesartan in Their Combined Dosage Form

A simple, rapid, and highly selective RP-HPLC method was developed for the simultaneous determination of Azelnidipine (AZL) and Olmesartan (OLM) drug substances in the fixed dosage strength of 16 mg and 20 mg, respectively. Effective chromatographic separation was achieved using a Hypersil GOLD C18 column (150 mm × 4.6 mm internal diameter, 5 μm particle size) with a mobile phase composed of methanol, acetonitrile, and water in the ratio of 40:40:20 (by volume). The mobile phase was pumped using a gradient HPLC system at a flow rate of 0.5 mL/min, and quantification of the analytes was based on measuring their peak areas at 260 nm. The retention times for Azelnidipine and Olmesartan were about 8.56 and 3.04 min, respectively. The reliability and analytical performance of the proposed HPLC procedure were statistically validated with respect to system suitability, linearity, ranges, precision, accuracy, specificity, robustness, detection, and quantification limits. Calibration curves were linear in the ranges of 2–48 μg/mL for Azelnidipine and 2.5–60 μg/mL for Olmesartan with correlation coefficients >0.990. The proposed method proved to be selective and stability-indicating by the resolution of the two analytes from the forced degradation (hydrolysis, oxidation, and photolysis) products. The validated HPLC method was successfully applied to the analysis of AZL and OLM in their combined dosage form