Cumulative Percentage Drug Release Research Articles

Formulation and Optimization of 5-Fluorouracil Loaded Chitosan Nanoparticles Employing Central Composite Design

5-Fluorouracil (5-FU) is a hydrophilic drug with short plasma half-life. The objective of the current study was to prepare and optimize 5-FU loaded chitosan nanoparticles (CNPs) for controlled release. The nanoparticles were prepared by ionic gelation of chitosan with tripolyphosphate anions. A 23 central composite design (CCD) was employed to study the influence of formulation variables - concentration of Chitosan (X1), the concentration of sodium tripolyphosphate (NaTPP) (X2) and volume of NaTPP (X3) on the cumulative percentage of drug release. The relationship between the dependent and independent variables was further elucidated using multiple linear regression analysis (MLRA) and Pareto chart. The results show that cumulative percent of 5-FU release was highest and lowest at high levels of X1, X2, and low level of X3, and high level of X1, and low levels of X2 and X3, respectively. The optimized nanoparticles were studied morphologically by transmission electron microscopy (TEM) which showed separated and non-aggregated nanoparticles with spherical shapes and smooth surfaces. The mean particle size, entrapment efficiency and loading capacity of the optimal CNPs were found to be 109.6±2.28 nm, 83.84±1.46%, and 37.76±3.41%, respectively. Nanoparticles revealed a fast release during the first hour followed by a more gradual drug release during a 24-h period following a non-Fickian diffusion process. Analysis of variance (ANOVA) was applied on cumulative percent of drug release to study the fitting and significance of model. The estimated model may be further utilized as response surface for cumulative percent of drug release from nanoparticles. The 5-FU loaded CNPs optimized using CCD showed good entrapment efficiency and controlled release as well as can reduce dosing frequency, decrease side effects and improve patient compliance.

DESIGN AND CHARECTERIZATION OF NOVEL TRANSDERMAL THERAPEUTIC SYSTEMS OF FELODIPINE

Felodipine is an effective calcium channel blocker, mainly used in the treatment of hypertension and angina pectoris. To overcome the low oral bioavailability of felodipine, the present work was designed to develop transdermal therapeutic system for felodipine using the polymer blend of eudragit RL 100 (ERL) / RS 100 (ERS) by solvent casting method and to study the effect of polymer composition, plasticizer and permeation enhancer on the physico-mechanical and in-vitro drug release characteristics of the film. Dibutyl phthalate (DBP) and oleic acid (OA) were used as plasticizer and permeation enhancer respectively. Different formulations with varied concentration of polymers, plasticizers and permeation enhancers were done and optimization of the concentration of formulation components was performed. Incorporation of DBP improved the flexibility, folding endurance and handling properties of the films. There was no significant difference in the drug content among patches indicating the uniformity in drug content. Increasing the concentration of ERL, and the presence of plasticizer were found to increase the in vitro drug release of the films.  The patches were also evaluated for ex vivo skin permeation using human cadaver skin. The presence of OA produced significant increase in the flux and permeability constant. The formulation with ERL: ERS ratio 1:4, 2% w/w OA as permeation enhancer and 20% w/w DBP as plasticizer showed the best results which exhibited the cumulative percentage of drug release of 75.73 ± 2.179 % and the cumulative amount of drug permeation across skin of 4321 ± 11.533 µg/cm2 in 24 hrs. Drug-excipient interaction studies were carried out using DSC and IR technique; films indicated no chemical interaction between drug and excipient. The results of the skin irritation studies showed no noticeable irritancy on rabbit skin indicating the skin compatibility of the drug as well as polymer. An attempt was made to develop the complete transdermal system of the drug by using backing membrane and release liner. Key-words: Transdermal Therapeutic System, Felodipine, Eudragit, Dibutyl Phthalate, Skin Permeation

Optimization of thermosensitive chitosan hydrogels for the sustained delivery of venlafaxine hydrochloride

Chitosan/glycerophosphate disodium (GP) thermosensitive hydrogels were prepared for the sustained delivery of venlafaxine hydrochloride (VH) and optimization of this formulation was mainly studied. Release mechanism was investigated by applying various mathematical models to the in vitro release profiles. Overall, drug release from the hydrogels showed best fit in first-order model and drug release mechanism was diffusion-controlled release. Optimization of VH chitosan/GP thermosensitive hydrogels was conducted by using a three-level three-factorial Box-Behnken experimental design to evaluate the effects of considered variables, the strength of the formulation, chitosan concentration and GP amount, on the selected responses: cumulative percentage drug release in 1h, 24h and the rate constant. It presented that higher strength and GP concentration resulted in higher initial release and rate constant, which supported the hypothesis that the kinetic gelation mechanism of this system was nucleation and growth. Drug release profiles illustrated that controlled drug delivery could be obtained over 24h, which confirmed the validity of optimization. In vivo pharmacokinetic study was investigated and it demonstrated that compared with VH solution, chitosan/GP thermosensitive hydrogels had a better sustained delivery of VH.

Osmotically Regulated Floating Asymmetric Membrane Capsule for Controlled Site-Specific Delivery of Ranitidine Hydrochloride: Optimization by Central Composite Design

A nondisintegrating, floating asymmetric membrane capsule (FAMC) was developed to achieve site-specific osmotic flow of a highly water-soluble drug, ranitidine hydrochloride (RHCl), in a controlled manner. Solubility suppression of RHCl was achieved by the common ion effect, using optimized coated sodium chloride as a formulation component. The capsular wall of FAMC was prepared by the phase inversion process wherein the polymeric membrane was precipitated on glass pins by dipping them in a solution of cellulose acetate followed by quenching. Central composite design was utilized to investigate the influence of independent variables, namely, level(s) of membrane former, pore former, and osmogen, on percent cumulative drug release (response). The release mechanism of RHCl through FAMC was confirmed as osmotic pumping. The asymmetry of the membrane was characterized by scanning electron microscopy that revealed a dense nonporous outer region of membrane supported by an inner porous region. Differential scanning calorimetry indicated no incompatibility between the drug and excipients. In vitro drug release in three biorelevant media, pH2.5 (low fed), pH4.5 (intermediate fed), and pH6.5 (high fed), demonstrated pH-independent release of RHCl (P > 0.05). Floating ability for 12h of the optimized FAMC9 was visually examined during the in vitro release studies that showed maximal drug release with zero-order kinetics (r (2) = 0.9991). Thus, a novel osmotically regulated floating capsular system was developed for site-specific delivery of RHCl.

DESIGN OF ORALLY DISINTEGRATING TABLET OF HYDROCHLORTHIAZIDE AND IT’S EVALUATION

The aim of present work was to show the effect of various superdisintegrant on the disintegration time and in vitro drug release rate. In this study, an attempt had been made to prepare orally disintegrating t ablets of the Hydrochlorthiazide using co - processed super disintegrant following direct compression method. Sodium starch glycolate, crospovidone and starch were used in different concentrations as the super disin tegrant. The tablets were evaluated for dia meter, thickness, hardness, friability, weight variation, wetting time, disintegration time, dispersion time, drug content an d in vitro dissolution studies. Friability value of none of the formulation exceeds 0.245 %. The dispersion time of all Formulatio n were found to be in between 17.95(±0.06) to 55.61(±0.06) seconds. The we tting time of all the tablets was in the range 25.70 - 52.70 second s . Overall, the formulation A5 containing 4 % w/w of co - processed superdisintegrants (1:1 mixture of crospovidone a nd sodium starch glycolate) was found to be promising and has shown an in vitro dispersion time 17.95 sec. , wetting time 21.14 sec and disintegration time 17.05 sec. Percentage cumulative drug release of formulation A5 was found to be 98.51% that is maximu m % drug release than other formulation. Formulation A5 containing 4%w/w of co - processed superdisintegrant (1:1 mixture of Crospovidone and sodium Starch glycolate) , using direct compression method was found to be the best formulation that has minimum di sintegration time, wetting time hence this formulation was selected for In - vitro dissolution study and more than 95% drug was dissolved within 15 min.

Product Development Studies on Surface-Adsorbed Nanoemulsion of Olmesartan Medoxomil as a Capsular Dosage Form

The present study aimed at development of capsular dosage form of surface-adsorbed nanoemulsion (NE) of olmesartan medoxomil (OLM) so as to overcome the limitations associated with handling of liquid NEs without affecting their pharmaceutical efficacy. Selection of oil, surfactant, and cosurfactant for construction of pseudoternary phase diagrams was made on the basis of solubility of drug in these excipients. Rationally selected NE formulations were evaluated for percentage transmittance, viscosity, refractive index, globule size, zeta potential, and polydispersity index (PDI). Formulation (F3) comprising of Capmul MCM® (10% v/v), Tween 80® (11.25% v/v), polyethylene glycol 400 (3.75% v/v), and double-distilled water (75% v/v) displayed highest percentage cumulative drug release (%CDR; 96.69 ± 1.841), least globule size (17.51 ± 5.87nm), low PDI (0.203 ± 0.032), high zeta potential (-58.93 ± 0.98mV), and hence was selected as the optimized formulation. F3 was adsorbed over colloidal silicon dioxide (2ml/400mg) to produce free-flowing solid surface-adsorbed NE that presented a ready-to-fill capsule composition. Conversion of NE to surface-adsorbed NE and its reconstitution to NE did not affect the in vitro release profile of OLM as the similarity factor with respect to NE was found to be 66% and 73% respectively. The %CDR after 12h for optimized NE, surface-adsorbed NE, and reconstituted NE was found to be 96.69 ± 0.54, 96.07 ± 1.76, and 94.78 ± 1.57, respectively (p > 0.05). The present study established capsulated surface-adsorbed NE as a viable delivery system with the potential to overcome the handling limitations of NE.

Moxifloxacin Loaded Polymeric Nanoparticles for Sustained Ocular Drug Delivery


 Efficient drug delivery to the ocular region is a challenging goal. Only a very small amount (about l-3%) of the dosage actually penetrates through the cornea and reaches intraocular tissues. To overcome these problems of conventional dosage forms, novel drug delivery systems like nanoparticles were designed. Moxifloxacin-loaded poly (lactic-co-glycolic acid) nanosuspension was prepared with the aim of providing sustained effect for ocular delivery for 24 hours. Nanosuspensions were prepared by nanoprecipitation method using poly(lactic-co-glycolic acid) and evaluated for particle size, surface morphology, zeta potential, drug entrapment efficiency, in vitro release and ex vivo transcorneal permeability, and were compared with marketed products. Microbiological efficacy was tested against Staphylococcus aureus and Pseudomonas aeroginosa using cup plate method. Spherical uniform particles (202.5 nm) with a polydispersity index of 0.226 and negative zeta potential (– 25.45 mV) were obtained for MF4 (drug to polymer ratio 1:0.4). Drug entrapment efficiency for MF4 was found to be 83.1%. The cumulative percent drug release for formulation MF4 after 24 hours was 86.1%, showing a sustained effect in controlling the bacterial conjunctivitis thereby avoiding frequent administration of dosage. MFX-loaded PLGA nanoparticles (MF4) showed a significantly higher drug permeation capability compared to the commercial marketed eye drops in ex vivo transcorneal permeation studies and also showed better antimicrobial efficacy compared to the marketed formulation. The results indicate that Moxifloxacin-loaded PLGA nanosuspension could be utilized as a potential drug delivery system for sustained release in ophthalmic application.

Development of Novel Gastroretentive Floating Particulate Drug Delivery System of Gliclazide

The objective of present project was to improve the dissolution profile of gliclazide by developing floating alginate beads using various biodegradable polymers like gelatin, pectin and hydroxypropylmethylcellulose (HPMC). The floating beads were prepared by a simple ionotropic gelatin method using calcium carbonate as gas generating agent. The developed beads were characterized by Fourier transform infrared spectroscopy analysis, differential scanning calorimetry, X-ray diffraction analysis and scanning electron microscopy (SEM). The prepared beads showed good in vitro floatation, which was dependent on the concentration of gas-forming agent. SEM photomicrographs confirmed that the developed beads were spherical in shape and had particle size in the range of 730 to 890 μm. The incorporation efficiency was found to be in the range of 59.96 to 85.1%. The cumulative percent drug release from the beads after 10 h dissolution study at pH 1.2 and pH 5.8 was in the range of 33 to 46% and 82 to 95% respectively. The concentration of the gas generating agent was found to influence the release rate. The mechanism of drug release was Fickian diffusion with swelling. The in vivo sub-acute hypoglycemic study in high fat diet induced diabetic C57BL/6J mice demonstrated significant (p < 0.05) hypoglycemic effect over a period of 12 h and 24 h, respectively, with HPMC and pectin beads. A significant (p & 0.05) reduction in fasting and non-fasting blood glucose levels, reduction in fasting plasma insulin level and a significant improvement in glucose tolerance were observed in animals treated with formulations. The developed beads were suitable carriers for improving the systemic absorption of gliclazide and maintaining reduced blood glucose levels.

Enteric Coated Guar Gum Microspheres of Ornidazole for Colonic Delivery

Enteric-coated guar gum microspheres of ornidazole aimed for colon drug delivery have been developed. The influence of core to coat ratio was investigated upon the encapsulation efficiency, swelling, weight loss and drug release behavior. The SEM was used to characterize the surface of these microspheres. Drug–polymer interactions were studied by differential scanning calorimetry and X-ray diffractometry. Enteric coating with Eudragit® S100 enabled maintenance of microspheres integrity until its expected arrival to colon. The in vitro drug release was investigated using USP dissolution rate test paddle type apparatus in different simulated mediums. Only 10 % of drug was release after 5 h while after 8 h (in PBS pH 7.5) a significant increase in percent cumulative drug release (85 %) was observed. In medium containing rat cecal content (pH 7.0) i.e. the amount of the drug released from the formulation was found to be 68 % and ~ 78.3 % with 2 % and 4% w/v cecal matter. Drug release in presence of culture of Bacteriodes ovatus was found to be 77 %. Ornidazole release kinetics corresponds best to zero order model and drug release mechanism was diffusion and swelling controlled. The significance of differences was evaluated by analysis of variance (ANOVA). Differences were considered statistically significant at P < 0.05. Keywords: Enteric coating, ornidazole, guar gum, eudragit® S100, microspheres, rat cecal contents, bacterial culture, DSC, XRD

Formulation, characterization and in vitro–in vivo evaluation of flurbiprofen-loaded nanostructured lipid carriers for transdermal delivery

Flurbiprofen is used in the treatment of arthritis. However, its multiple dosing due to short elimination half life is a concern for such treatment. This work aims to develop nanostructured lipid carriers (NLCs) of flurbiprofen and evaluate their potential for transdermal delivery. The NLCs were prepared by the optimized o/w emulsification-homogenization-sonication technique using coconut oil (liquid lipid). The NLCs were found to be spherical with uniform size (214 nm). The entrapment efficiency and zeta potential were 92.58% and −30.70 mV, respectively. Differential scanning calorimetry (DSC) showed the amorphous state of flurbiprofen encapsulated in NLCs. The percentage cumulative drug release through the excised rat skin from NLCs was biphasic and significantly prolonged compared with the commercial gel. DSC of the treated skin indicated that the NLCs penetrate into follicles of the skin and accumulate in the dermis. The bioavailability of flurbiprofen from NLCs was more than 1.7-fold that of the commercial gel. The NLCs showed a quick onset and sustained anti-inflammatory effect over period of 24 h for carrageenan-induced rat paw edema than the commercial gel. The stability data revealed that the NLCs were more stable when stored at 5°C. In conclusion, prepared NLCs have potential for skin targeting and sustained drug release.

Formulation and characterization of ketoprofen liquisolid compacts by Box-Behnken design

Introduction:Liquisolid technique is used in delivery of lipophilic and poorly water soluble drugs through oral route. It involves dissolving water insoluble drugs in nonvolatile solvents and converting into acceptably flowing and compressible powders. The objective of the present work was to enhance the dissolution rate of ketoprofen using microcrystalline cellulose as carrier, aerosil 200 as coating material, and polyethylene glycol as nonvolatile water miscible liquid vehicle.Materials and Methods:The drug concentration was kept constant in all formulations at 40% w/w. Optimization was carried out using Box–Behnken design by selecting liquid load factor, amount of coating material, and amount of magnesium oxide as independent variables; cumulative percentage drug release and angle of repose were considered as dependent variables.Results:The Fourier transform infrared (FTIR) and differential scanning calorimetry (DSC) studies revealed that there was no possible interaction between drug and tablet excipients. Prepared ketoprofen liquisolid tablets were evaluated for hardness, weight variation, friability, in-vitro disintegration time, drug content uniformity, and in-vitro dissolution studies. The optimized formulation yielded the response values, which were very close to the predicted values. The accelerated stability studies conducted showed that liquisolid tablets were not affected by ageing and there were no appreciable changes in the drug content.

Development and Characterization of Mouth Dissolving Tablet of Zolmitriptan

ObjectiveTo formulate and Characterize Mouth Dissolving Tablet of Zolmitriptan to produce the intended benefits. MethodsTablets were prepared using a direct compression method employing superdisintegrants such as Kyron T-314, Crospovidone, Croscarmellose Sodium, and Sodium Starch Glycolate. Tablets of Zolmitriptan prepared using Kyron T-314 exhibited the least friability and disintegration time 35 seconds. To decrease the disintegration time further, a sublimation technique was used along with the superdisintegrants for the preparation of Mouth Dissolving Tablet (MDTs). The addition of camphor as a subliming agent lowered the disintegration time 10 seconds further, but the percent friability was increased. A 32 full factorial design was employed to study the joint influence of the amount of superdisintegrant (Kyron T-314) and the amount of sublimating agent (Camphor) on the percent of friability and the disintegration time. ResultsThe results of multiple linear regression analysis revealed that an effective MDT of Zolmitriptan requires higher percentages of Kyron T-314 and camphor should be used. The approach using the optimization technique helped to produce a detailed understanding effect of formulation parameters. An optimized formulation was found to have good hardness, wetting time, disintegration time. Release kinetic model study indicated that all the formulations follow zero order kinetics. It also indicated that batch F1, F2, F5 and F8 releases the drug at constant rate as well as fast rate as per the Weibull model which was also confirmed by Hixson-Crowell model. Stability studies indicated that there are no significant changes in hardness, Percentage friability, drug content and in-vitro disintegration time and cumulative percentage drug release. ConclusionsThus, it was concluded that by adopting a systematic formulation approach, Zolmitriptan Mouth dissolving tablet could be formulated using superdisintegrants in combination with a vacuum-drying technique for improved therapeutic efficacy.

Transfersomes: A Novel Vesicular Carrier for Enhanced Transdermal Delivery of Sertraline: Development, Characterization, and Performance Evaluation

The aim of the present study was to investigate transfersomes as a transdermal delivery system for the poorly soluble drug, sertraline, in order to overcome the troubles associated with its oral delivery. Different transfersomal formulations were prepared with non-ionic surfactant (span 80), soya lecithin, and carbopol 940 by the rotary evaporation sonication method. The prepared formulations were characterized for light microscopy, particle size analysis, drug entrapment, turbidity, drug content, rheological studies, in vitro release, ex vivo permeation, and stability studies. The optimized formulation was evaluated for in vivo studies using the modified forced swim model test. FTIR studies showed compatibility of the drug with excipients. The result revealed that sertraline in all of the formulations was successfully entrapped with uniform drug content. Transfersomal gel containing 1.6% of the drug and 20% of span 80 was concluded to be the optimized formulation (EL-SP4), as it showed maximum drug entrapment (90.4±0.15%) and cumulative percent drug release(73.8%). The ex vivo permeation profile of EL-SP4 was compared with the transfersomal suspension, control gel, and drug solution. The transfersomal gel showed a significantly higher (p<0.05) cumulative amount of drug permeation and flux along with lower lag time than the drug solution and drug gel. It also owed to better applicability due to the higher viscosity imparted by the gel rather than the transfersomal suspension, and no skin irritation was observed. The modified forced swim test in mice revealed that the transfersomal gel had better antidepressant activity as compared to the control gel. Thus, the study substantiated that the transfersomal gel can be used as a feasible alternative to the conventional formulations of sertraline with advanced permeation characteristics for transdermal application.

Formulation of Diclofenac tablets for rapid pain relief

ObjectiveTo develop fast dissolving tablets of diclofenac in order to get fast relief from pain. MethodsFast dissolving tablets of diclofenac potassium were prepared by direct compression method using Indion 214, Indion 234, Indion 244 and croscarmellose as superdisintegrants. Microcrystalline cellulose was used as diluents and mannitol, as sweetening agent. Tablets were evaluated for weight variation; weight variation of all the formulations was observed which were within the acceptable limit for uncoated tablets as per United States Pharmacopoeia. ResultsMechanical strength, the hardness of tablets was determined and was found to be in the range of 6.4 to 7.13 Kg/cm2. In vitro disintegration time, the formulation containing indion214, indion234 andindion244 showed 34,31and 39 seconds value for in vitro disintegration respectively. Wetting time for all the formulations was found to be (4.425±0.25) to (5.75±2.25) seconds and the cumulative percentage drug release of formulations FD1- FD5. It was observed that in first 10 minutes, only 12.89% of drug was release from formulation FD5 without using superdisintegrants and while it was 88.56% in the case of formulation FD2. At the end of 24 minutes only 85.42 % of drug was released from the control tablet formulation FD5 whereas the cumulative release from other formulations FD1 and FD4 at the end of 12 minutes was 89.52 %and 79.29%, respectively. The results of in vitro disintegration time show that formulation containing Indion 244, showed the disintegration time of 29.66 seconds. ConclusionsIndion 244 was found to have super disintegrant property the addition technique is a best method for preparing fast dissolving tablets for rapid pain mangment.

Formulation and evaluation of controlled release ocular inserts of betaxolol hydrochloride

–Betaxolol Hydrochloride is a cardio selective β1 adrenergic receptor blocking agent used in the treatment of chronic open angle glaucoma and ocular hypertension In the present study, an attempt was made to formulate Betaxolol HCl ocular inserts. In matrix type the formulations for Betaxolol containing 10%, 12%, and 14% w/v of Gelatin, 1%, 1.5%, 2%, 2.5% and 3% w/v for Chitosan were prepared by solvent casting method and plasticizer were used in different concentration for smoothing texture of the ocular inserts. The prepared batches of ocular inserts were evaluated for weight variation thickness, drug content uniformity, swelling index. An increase in average weight and thickness is due to increase in polymer concentration. IR spectral studies were performed to confirm the interaction of drug with excipients. All formulations were tested for in vitro drug release (Simulated tear fluid) by vial method. The formulations GH8 and C5 show a maximum cumulative percentage drug release of 98.76% and 97.72% at the end of 12 th hrs, respectively. The drug release in all formulations decreases as the polymer concentration increases. The dissolution data of formulation were subjected to first order, Higuchi’s, and peppas equations. Drug release from the ocuserts by diffusion controlled mechanism. No significant change in the drug content and physical features was observed during storage at 25 0 C/60% RH and 40 0 C/75% RH for the selected formulation for three months. Keywords––Betaxolol Hydrochloride, Chitosan, Gelatin, Ocular inserts.

Development and physico-mechanical characterisation of lyophilised chitosan wafers as potential protein drug delivery systems via the buccal mucosa

Lyophilised wafers from chitosan have been developed as potential protein drug delivery systems via the buccal mucosa. Wafers were prepared by lyophilising aqueous gels of the polymer incorporating varying concentrations of glycerol as plasticizer and d-mannitol as cryoprotectant. The different formulations were characterised by their physico-mechanical properties in order to select the optimum system for further development. The optimised formulation with 6.5 mg each of both plasticizer and cryoprotectant was loaded with bovine serum albumin and lyophilised with or without annealing. Differential scanning calorimetry was used to determine the appropriate lyophilisation cycle by evaluating thermal events before lyophilisation and possible phase separation of bovine serum albumin after lyophilisation. Texture analysis was employed to investigate the in vitro mucoadhesive properties in tensile mode, residual moisture content by thermo-gravimetric analysis while hydration capacity and drug release studies were performed in 0.1 M phosphate buffered saline. Microscopic architecture and crystallinity were examined using scanning electron microscopy and X-ray diffractometry respectively. The ease of hydration, in vitro mucoadhesive characteristics, microscopic architecture and BSA release were influenced by the annealing process. A 7 h cumulative percentage drug release of 91.5% and 80.1% was observed for the annealed and non-annealed wafers respectively. The results showed the potential of employing lyophilised chitosan wafers for buccal mucosa delivery of protein based drugs.

Colon-Specific Microparticles of Piroxicam: Formulation and Optimization Using 32 Factorial Design

The aim of the present study was to prepare and evaluate colon-specific microparticles of piroxicam by oil/water emulsion solvent evaporation method. A 32 factorial design was employed to study the combined influence of two independent variables amount of piroxicam (X1) and amount of eudragit S-100 (X2) on dependent variables, encapsulation efficacy (Y1), percentage cumulative drug release at the fifth hour (Y2), and percentage cumulative drug release at the tenth hour (Y3). The microparticles were evaluated for micromeritic properties and drug release studies. Drug–polymer interaction was determined by differential scanning calorimeter, x-ray powder diffraction. The surface morphology and spherocity was studied by scanning electron microscopy. The developed piroxicam microparticles showed desired colon-specific delivery.

Factorial design-based development of measlamine microspheres for colonic delivery

For treating colonic diseases, conventional oral drug delivery systems are not effective, as they fail to reach the appropriate site of action. Thus, there is a need to develop effective and safe therapy for the treatment of colonic disorders. The aim of the present study was to design a colon-specific delivery system for an anti-inflammatory drug, mesalamine, with minimal degradation and optimum delivery of the drug with relatively higher local concentration, which may provide more effective therapy for inflammatory bowel disease including Crohn disease and ulcerative colitis. Factorial designs (four factors and two levels) for eudragit S-100 (pH-dependent polymer)-coated, pectin (natural polysaccharides)-based microspheres of mesalamine were constructed and conducted in a fully randomized manner to study all possible combinations. Based on the desirability function formulation, F14 was found to be the best formulation. The overall desirability coefficient of formulation F14 was found to be 0.825. The formulation F14 was subjected to in vitro release studies, and the results were evaluated kinetically and statistically. The microspheres started releasing the drug at the beginning of 7th hour, which corresponds to the arrival time at proximal colon. The cumulative percent drug release for formulation F14 at the end of 16 h was found to be 98%. The release kinetics showed that the release followed the Higuchi model, and the main mechanism of drug release was diffusion. The study presents a new approach for colon-specific drug delivery.

Formulation and evaluation of floating oral in situ gelling system of amoxicillin.

Purpose. Effective Helicobacter pylori eradication requires delivery of the antibiotic locally in the stomach. High dose of amoxicillin (750 to 1000 mg) is difficult to incorporate in floating tablets but can easily be given in liquid dosage form. Keeping the above facts in mind, we made an attempt to develop a new floating in situ gelling system of amoxicillin with increased residence time using sodium alginate as gelling polymer to eradicate H. pylori. Methods. Floating in situ gelling formulations were prepared using sodium alginate, calcium chloride, sodium citrate, hydroxypropyl methyl cellulose K100, and sodium bicarbonate. The prepared formulations were evaluated for solution viscosity, floating lag time, total floating time, and in vitro drug release. The formulation was optimized using a 32 full factorial design. Dissolution data were fitted to various models to ascertain kinetic of drug release. Regression analysis and analysis of variance were performed for dependent variables. Results. All formulations (F 1–F 9) showed floating within 30 s and had total floating time of more than 24 h. All the formulations showed good pourability. It was observed that concentration of sodium alginate and HPMC K100 had significant influence on floating lag time, cumulative percentage drug release in 6 h and 10 h. The batch F 8 was considered optimum since it showed more similarity in drug release (f 2 = 74.38) to the theoretical release profile. Conclusion. Floating in situ gelling system of amoxicillin can be formulated using sodium alginate as a gelling polymer to sustain the drug release for 10 to 12 h with zero-order release kinetics.

Novel microbially triggered colon specific delivery system of 5-Fluorouracil: Statistical optimization, in vitro, in vivo, cytotoxic and stability assessment

The present study aimed to statistically optimize a colon specific formulation of 5-Fluorouracil for the treatment of colon cancer. A 3 2 full factorial design was used for optimization. The independent variables employed were amount of pectin and amount of starch paste, each at three levels. The evaluated responses were hardness, percent cumulative drug release (% CDR) at 5th h and t 90% (time required for 90% of drug release). Drug release studies were carried out using change over media [pH 1.2, 7.4 and 6.5 in presence of 4% (w/v) rat caecal contents]. The optimized formulation was subjected to in vivo roentgenographic studies in New Zealand white rabbits to analyze the in vivo behaviour of the developed tablets. This formulation was also evaluated for cytotoxic potential using HT-29 human colon cancer cell lines. Pharmacokinetic studies in New Zealand white rabbits were conducted to determine the extent of systemic exposure provided by the developed formulation in comparison to an immediate release tablet. The optimized formulation consisting of pectin (66.67%, w/w) and starch paste (15%, w/w) released negligible amount of drug at pH 1.2 and pH 7.4 whereas significant ( p < 0.05) drug release was observed at pH 6.5 in presence of 4% (w/v) rat caecal contents. Roentgenographic studies corroborated the in vitro observations, thus providing the “proof of concept”. Pharmacokinetic studies revealed significant reduction in systemic exposure and cytotoxicity studies demonstrated enhanced cellular uptake of drug by the developed formulation. Shelf life of the formulation was found to be 2.83 years. The results of the study established pectin-based coated matrix tablet to be a promising system for the colon specific delivery of 5-FU so as to treat colon carcinoma.