Modification of theophylline release with alginate gel formed in hard capsules

The aim of this work was to establish whether alginate gel formed spontaneously in hard gelatin capsules which modifies release of a model drug, theophylline. The effects of the alginate composition, the calcium addition, and the dissolution medium on drug release were also investigated. After the capsule shell dissolved in water, at neutral pH the gel layer of sodium alginate was formed immediately as the sodium alginate hydrated and swelled on contact with the aqueous medium. In acidic pH, the contents remained intact and the matrix shape was the same. Theophylline release from capsules containing different grades of alginate demonstrated different release patterns, depending on alginate composition and the pH of the medium. The capsules containing sodium/calcium salts of alginate showed the slowest drug release at neutral pH but the fastest in acidic medium. The presence of calcium acetate in the formulations influenced the drug release kinetics. The drug release in acidic medium showed a non-Fickian diffusion-controlled release, while those in water at neutral pH exhibited a Super Case II transport mechanism. The study also provides evidence that the behavior of alginate in forming the hydrated gel layer may explain the drug release behavior at different pHs. Published: July 6, 2007     

Wax-incorporated Emulsion Gel Beads of Calcium Pectinate for Intragastric Floating Drug Delivery

The purpose of this study was to prepare wax-incorporated pectin-based emulsion gel beads using a modified emulsion-gelation method. The waxes in pectin–olive oil mixtures containing a model drug, metronidazole, were hot-melted, homogenized and then extruded into calcium chloride solution. The beads formed were separated, washed with distilled water and dried for 12 h. The influence of various types and amounts of wax on floating and drug release behavior of emulsion gel beads of calcium pectinate was investigated. The drug-loaded gel beads were found to float on simulated gastric fluid if the sufficient amount of oil was used. Incorporation of wax into the emulsion gel beads affected the drug release. Water-soluble wax (i.e. polyethylene glycol) increased the drug release while other water-insoluble waxes (i.e. glyceryl monostearate, stearyl alcohol, carnauba wax, spermaceti wax and white wax) significantly retarded the drug release. Different waxes had a slight effect on the drug release. However, the increased amount of incorporated wax in the formulations significantly sustained the drug release while the beads remained floating. The results suggest that wax-incorporated emulsion gel beads could be used as a carrier for intragastric floating drug delivery.     

Stomach-specific drug delivery of 5-fluorouracil using floating alginate beads

A multiple-unit-type oral floating dosage form (FDF) of 5-fluorouracil (5-FU) was developed to prolong gastric residence time, target stomach cancer, and increase drug bioavailability. The floating bead formulations were prepared by dispersing 5-FU together with calcium carbonate into a mixture of sodium alginate and hydroxypropyl methylcellulose solution and then dripping the dispersion into an acidified solution of calcium chloride. Calcium alginate beads were formed, as alginate undergoes ionotropic gelation by calcium ions and carbon dioxide develops from the reaction of carbonate salts with acid. The evolving gas permeated through the alginate matrix, leaving gas bubbles or pores, which provided the beads buoyancy. The prepared beads were evaluated for percent drug loading, drug entrapment efficiency, image, surface topography, buoyancy, and in vitro release. The formulations were optimized for different weight ratios of gas-forming agent and sodium alginate. The beads containing higher amounts of calcium carbonate demonstrated instantaneous, complete, and excellent floating ability over a period of 24 hours. The optimized formulation was subjected to in vivo antitumor studies to check the therapeutic efficacy of the floating dosage forms containing 5-FU against benzo(a)pyrene-induced stomach tumors in albino female mice (Balb/C strain). The multiple-bead FDF was found to reduce the tumor incidence in mice by 74%, while the conventional tablet dosage form reduced this incidence by only 25%. Results indicate that FDF performed significantly better than the simple tablet dosage form. Published: June 22, 2007     

Formulation of liposomes gels of paeonol for transdermal drug delivery by Box-Behnken statistical design

The aim of this study was to design and optimize a transdermal liposomes gel formulation for paeonol (PAE). A three-factor, three-level Box-Behnken design was used to derive a second-order polynomial equation to construct three-dimensional (3-D) contour plots for prediction of responses. Independent variables studied were the DC-Chol concentration (X₁), molar ratio of lipid/drug (X₂), and the polymer concentration (X₃), and the levels of each factor were low, medium, and high. The dependent variables studied were the encapsulation efficiency (%EE) of PAE (Y₁), flux of PAE (Y₂), and viscosity of the gels (Y₃). Response surface plots were drawn and statistical validity of the polynomials was established to find the compositions of optimized formulation, which was evaluated using the Franz diffusion cell. The %EE of PAE increased proportionally with the molar ratio of lipid/drug, but decreased with polymer concentration, whereas the flux of PAE increased proportionally with polymer concentration and the DC-Chol concentration. The viscosity of gels increased with the polymer concentration. Gels showed a non-Fickian diffusion release mechanism for PAE, and the in vitro release profiles were fit for Higuchi’s order model. The design demonstrated the role of the derived polynomial equation and 3-D contour plots in predicting the values of dependent variables for the preparation and optimization of gel formulation for transdermal drug release.     

Statistical Approach for Assessing the Influence of Calcium Silicate and HPMC on the Formulation of Novel Alfuzosin Hydrochloride Mucoadhesive-Floating Beads as Gastroretentive Drug Delivery Systems

Multiparticulate floating drug delivery systems have proven potential as controlled-release gastroretentive drug delivery systems that avoid the "all or none" gastric emptying nature of single-unit floating dosage forms. An objective of the presence investigation was to develop calcium silicate (CaSi)/calcium alginate (Ca-Alg)/hydroxypropyl methylcellulose (HPMC) mucoadhesive-floating beads that provide time- and site-specific drug release of alfuzosin hydrochloride (Alf). Beads were prepared by simultaneous internal and external gelation method utilizing 3(2) factorial design as an experimental design; with two main factors evaluated for their influence on the prepared beads; the concentration of CaSi as floating aid (X (1)) and the percentage of HPMC as viscosity enhancer and mucoadhesive polymer (X (2)), each of them was tested in three levels. Developed formulations were evaluated for yield, entrapment efficiency, particle size, surface topography, and buoyancy. Differential scanning calorimetry, Fourier transform infrared spectroscopy, in vitro drug release, as well as in vitro mucoadhesion using rat stomach mucosal membrane were also conducted. Percentage yield and entrapment efficiency ranged from 57.03% to 78.51% and from 49.78% to 83.26%, respectively. Statistical analysis using ANOVA proved that increasing the concentration of either CaSi or HPMC significantly increased the beads yield. Both CaSi and HPMC concentrations were found to significantly affect Alf release from the beads. Additionally, higher CaSi concentration significantly increased the beads diameter while HPMC concentration showed significant positive effect on the beads mucoadhesive properties. CaSi/Ca-Alg/HPMC beads represent simple floating-mucoadhesive gastroretentive system that could be useful in chronopharmacotherapy of benign prostatic hyperplasia.     

Novel Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) for Oral Delivery of Cinnarizine: Design, Optimization, and In-Vitro Assessment

Due to its extreme lipophilicity, the oral delivery of cinnarizine (CN) encounters several problems such as poor aqueous solubility and pH-dependent dissolution, which result in low and erratic bioavailability. The current study aims to design self-nanoemulsifying drug delivery systems (SNEDDS) of CN that circumvent such obstacles. Equilibrium solubility of CN was determined in a range of anhydrous and diluted lipid-based formulations. Dynamic dispersion tests were carried out to investigate the efficiency of drug release and magnitude of precipitation that could occur upon aqueous dilution. Droplet sizes of selected formulations, upon (1:1,000) aqueous dilution, were presented. The optimal formulations were enrolled in subsequent dissolution studies. The results showed that increasing lipid chain length and surfactant lipophilicity raised the formulation solvent capacity, while adding co-solvents provoked a negative influence. The inclusion of mixed glycerides and/or hydrophilic surfactants improved the drug release efficiency. Generally, no significant precipitation was observed upon aqueous dilution of the formulations. Five formulations were optimal in terms of their superior self-emulsifying efficiency, drug solubility, dispersion characteristics, and lower droplet size. Furthermore, the optimal formulations showed superior dissolution profile compared to the marketed (Stugeron®) tablet. Most importantly, they could resist the intensive precipitation observed with the marketed tablet upon shifting from acidic to alkaline media. However, SNEDDS containing medium-chain mixed glycerides showed the highest drug release rate and provide great potential to enhance the oral CN delivery. Accordingly, the lipid portion seems to be the most vital component in designing CN self-nanoemulsifying systems.     

Design and Evaluation of Hydrophilic Matrix System Containing Polyethylene Oxides for the Zero-Order Controlled Delivery of Water-Insoluble Drugs

The aim of this study was to design a polyethylene oxide (PEO) binary hydrophilic matrix controlled system and investigate the most important influence(s) on the in vitro water-insoluble drug release behavior of this controlled system. Direct-compressed PEO binary matrix tablets were obtained from a variety of low viscosity hydrophilic materials as a sustained agent, using anhydrous drugs as a model drug. Water uptake rate, swelling rate, and erosion rate of matrices were investigated for the evaluation of the PEO hydrophilic matrix systems. The effect of the dose, the solubility of water-insoluble drug, and the rheology of polymers on in vitro release were also discussed. Based on the in vitro release kinetics study, three optimized PEO binary matrices were selected for further research. And, these PEO binary matrices had shown the similar release behavior that had been evaluated by the similarity factor f ₂. Further study indicated that they had identical hydration, swelling, and erosion rate. Moreover, rheology study exhibited the similar rheological equation of Herschel–Bulkley and their viscosity was also within the same magnitude. Therefore, viscosity plays the most important role to control drug release compared to other factors in PEO binary matrix system. This research provides fundamental understanding of in vitro drug release of PEO binary hydrophilic matrix tablets and helps pharmaceutical workers to develop a hydrophilic controlled system, which will effectively shorten the process of formulation development by reducing trial-and-error.     

Poloxamer 407-based intranasal thermoreversible gel of zolmitriptan-loaded nanoethosomes: formulation,optimization, evaluation and permeation studies

Zolmitriptan is the drug of choice for migraine, but low oral bioavailability (<50%) and recurrence of migraine lead to frequent dosing and increase in associated side effects. Increase in the residence time of drug at the site of drug absorption along with direct nose to brain targeting of zolmitriptan can be a solution to the existing problems. Hence, in the present investigation, thermoreversible intranasal gel of zolmitriptan-loaded nanoethosomes was formulated by using mucoadhesive polymers to increase the residence of the drug into the nasal cavity. The preparation of ethosomes was optimized by using 3² factorial design for percent drug entrapment efficiency, vesicle size, zeta potential, and polydispersity index. Optimized formulation E6 showed the vesicle size (171.67?nm) and entrapment efficiency (66%) when compared with the other formulations. Thermoreversible gels prepared by using poloxamer 407 showed the phase transition temperature at 32–33?°C which was in line with the nasal physiological temperature. The optimized ethosomes were loaded into the thermoreversible mucoadhesive gel optimized by varying concentrations of poloxamer 407, carbopol 934, HPMC K100, and evaluated for gel strength, gelation temperature, mucoadhesive strength, in vitro drug release, and ex vivo drug permeation, where G3 and G6 were found to be optimized formulations. In vitro drug release was studied by different kinetic models suggested that G3 (n?=?0.582) and G6 (n?=?0.648) showed Korsemeyer–Peppas (K_KP) model indicating non-Fickian release profiles. A permeation coefficient of 5.92 and 5.9?µg/cm² for G3 and G6, respectively, revealed very little difference in release rate after 24?h between both the formulations. Non-toxic nature of the gels on columnar epithelial cells was confirmed by histopathological evaluation.     

Vincristine-sulphate–loaded liposome-templated calcium phosphate nanoshell as potential tumor-targeting delivery system

Vincristine-sulfate–loaded liposomes were prepared with an aim to improve stability, reduce drug leakage during systemic circulation, and increase intracellular uptake. Liposomes were prepared by the thin-film hydration method, followed by coating with calcium phosphate, using the sequential addition approach. Prepared formulations were characterized for size, zeta potential, drug-entrapment efficiency, morphology by transmission electron microscopy (TEM), in vitro drug-release profile, and in vitro cell cytotoxicity study. Effect of formulation variables, such as drug:lipid ratio as well as nature and volume of hydration media, were found to affect drug entrapment, and the concentration of calcium chloride in coating was found to affect size and coating efficiency. Size, zeta potential, and TEM images confirmed that the liposomes were effectively coated with calcium phosphate. The calcium phosphate nanoshell exhibited pH-dependent drug release, showing significantly lower release at pH 7.4, compared to the release at pH 4.5, which is the pH of the tumor interstitium. The in vitro cytotoxicity study done on the lung cancer cell line indicated that coated liposomes are more cytotoxic than plain liposomes and drug solution, indicating their potential for intracellular drug delivery. The cell-uptake study done on the lung cancer cell line indicated that calcium-phosphate–coated liposomes show higher cell uptake than uncoated liposomes.     

Vincristine-sulphate-loaded liposome-templated calcium phosphate nanoshell as potential tumor-targeting delivery system

Vincristine-sulfate-loaded liposomes were prepared with an aim to improve stability, reduce drug leakage during systemic circulation, and increase intracellular uptake. Liposomes were prepared by the thin-film hydration method, followed by coating with calcium phosphate, using the sequential addition approach. Prepared formulations were characterized for size, zeta potential, drug-entrapment efficiency, morphology by transmission electron microscopy (TEM), in vitro drug-release profile, and in vitro cell cytotoxicity study. Effect of formulation variables, such as drug:lipid ratio as well as nature and volume of hydration media, were found to affect drug entrapment, and the concentration of calcium chloride in coating was found to affect size and coating efficiency. Size, zeta potential, and TEM images confirmed that the liposomes were effectively coated with calcium phosphate. The calcium phosphate nanoshell exhibited pH-dependent drug release, showing significantly lower release at pH 7.4, compared to the release at pH 4.5, which is the pH of the tumor interstitium. The in vitro cytotoxicity study done on the lung cancer cell line indicated that coated liposomes are more cytotoxic than plain liposomes and drug solution, indicating their potential for intracellular drug delivery. The cell-uptake study done on the lung cancer cell line indicated that calcium-phosphate-coated liposomes show higher cell uptake than uncoated liposomes.     

Investigation of factors influencing drug release using calcium alginate polymer

The effects of mixing, the sodium alginate concentration, and calcium chloride concentration on the release of sulphamethoxazole (model drug) impregnated in calcium alginate beads were investigated and evaluated. The release behaviour of the sulphamethoxazole from the calcium alginate beads was studied in a 0.1N HCl aqueous solution at 37v°C. The release rate of the sulphamethoxazole depends heavily on the type of mixers during the formation of the drug-alginate beads. The highest release rate was achieved when four-bladed rectangular agitator was used while the lowest release was achieved when magnetic stirrer was used. The amount of the released sulphamethoxazole varies slightly with the variation of the alginate concentration. The total release of sulphamethoxazole when 1% w/v solution of sodium alginate was used found to be 80% of the total drug content while 72% and 68% of the total drug content for 1.5% and 2% sodium alginate solutions. Three different calcium chloride concentrations were used (i.e., 5%, 10%, and 15% CaCl₂). The effect of the calcium chloride concentration on the release of the sulphamethoxazole is very pronounced.     

Statistical optimization of gastric floating system for oral controlled delivery of calcium

The development of an optimized gastric floating drug delivery system is described. Statistical experimental design and data analysis using response surface methodology is also illustrated. A central, composite Box-Wilson design for the controlled release of calcium was used with 3 formulation variables: X₁ (hydroxypropyl methylcellulose [HPMC] loading), X₂ (citric acid loading), and X₃ (magnesium stearate loading). Twenty formulations were prepared, and dissolution studies and floating kinetics were performed on these formulations. The dissolution data obtained were then fitted to the Power Law, and floating profiles were analyzed. Diffusion exponents obtained by Power Law were used as targeted response variables, and the constraints were placed on other response variables. All 3 formulation variables were found to be significant for the release properties (P<,05), while only HPMC loading was found to be significant for floating properties. Optimization of the formulations was achieved by applying the constrained optimization. The optimized formulation delivered calcium at the release rate of 40 mg/hr, with predicted n and T_50% values at 0.93 and 3.29 hours, respectively. Experimentally, calcium was observed to release from the optimized formulation with n and T_50% values of 0.89 (±0.10) and 3.20 (±0.21) hours, which showed an excellent agreement. The quadratic mathematical model developed could be used to further predict formulations with desirable release and floating properties.     

Studies on a novel doughnut-shaped minitablet for intraocular drug delivery

The objective of this study was to evaluate the effect of 2 independent formulation variables on the drug release from a novel doughnut-shaped minitablet (DSMT) in order to optimize formulations for intraocular drug delivery. Formulations were based on a 3(2) full-factorial design. The 2 independent variables were the concentration of Resomer (% wt/wt) and the type of Resomer grade (RG502, RG503, and RG504), respectively. The evaluated response was the drug release rate constant computed from a referenced marketed product and in vitro drug release data obtained at pH 7.4 in simulated vitreous humor. DSMT devices were prepared containing either of 2 model drugs, ganciclovir or foscarnet, using a Manesty F3 tableting press fitted with a novel central-rod, punch, and die setup. Dissolution data revealed biphasic drug release behavior with 55% to 60% drug released over 120 days. The inherent viscosity of the various Resomer grades and the concentration were significant to achieve optimum release rate constants. Using the resultant statistical relationships with the release rate constant as a response, the optimum formulation predicted for devices formulated with foscarnet was 70% wt/wt of Resomer RG504, while 92% wt/wt of Resomer RG503 was ideal for devices formulated with ganciclovir. The results of this study revealed that the full-factorial design was a suitable tool to predict an optimized formulation for prolonged intraocular drug delivery.     

PEGylated rosin derivatives: Novel microencapsulating materials for sustained drug delivery

The aim of this study was to investigate PEGylated rosin derivatives (PRDs) as microencapsulating materials for sustained drug delivery. PRDs (D1, D2, and D3) composed of a constant weight of rosin and varied amounts of polyethylene glycol (PEG) 400 and maleic anhydride were synthesized in the laboratory. Microparticles were prepared by the O/O solvent evaporation technique using the acetone/paraffin system. Diclofenac sodium (DFS) and diltiazem hydrochloride (DLTZ) were used as model drugs. The effect of the type of PRD, drug, PRD:drug ratio, viscosity of external phase, stirring speed, concentration of magnesium stearate (droplet stabilizer), and method of preparation on particle size, drug loading, and drug release profiles of microparticles was investigated. PRDs could produce discrete and spherical microspheres (with DFS) and microcapsules (with DLTZ). The drug loading value for microparticles was found to be in the range of 37.21% to 87.90%. The microparticle size range was 14 to 36 μm. The particle size and drug loadings of microparticles were substantially affected by the concentration of magnesium stearate and the type of drug, respectively. Most of the formulations could sustain the DFS and DLTZ release for 20 hours. DFS and DLTZ release from PRD microparticles followed Hixson-Crowell and first-order kinetics, respectively. The results suggest that PRDs can be used successfully to prepare discrete and spherical microparticles with DFS and DLTZ for sustained drug delivery. Published: June 22, 2007     

Controlled Release Hydrophilic Matrix Tablet Formulations of Isoniazid: Design and In Vitro Studies

The aim of the present investigation was to develop oral controlled release matrix tablet formulations of isoniazid using hydroxypropyl methylcellulose (HPMC) as a hydrophilic release retardant polymer and to study the influence of various formulation factors like proportion of the polymer, polymer viscosity grade, compression force, and release media on the in vitro release characteristics of the drug. The formulations were developed using wet granulation technology. The in vitro release studies were performed using US Pharmacopoeia type 1 apparatus (basket method) in 900 ml of pH 7.4 phosphate buffer at 100 rpm. The release kinetics was analyzed using Korsmeyer–Peppas model. The release profiles were also analyzed using statistical method (one-way analysis of variance) and f ₂ metric values. The release profiles found to follow Higuchi’s square root kinetics model irrespective of the polymer ratio and the viscosity grade used. The results in the present investigation confirm that the release rate of the drug from the HPMC matrices is highly influenced by the drug/HPMC ratio and viscosity grade of the HPMC. Also, the effect of compression force and release media was found to be significant on the release profiles of isoniazid from HPMC matrix tablets. The release mechanism was found to be anomalous non-Fickian diffusion in all the cases. In the present investigation, a series of controlled release formulations of isoniazid were developed with different release rates and duration so that these formulations could further be assessed from the in vivo bioavailability studies. The formulations were found to be stable and reproducible.     

Properties of pellets manufactured by wet extrusion/spheronization process using kappa-carrageenan: effect of process parameters

The aim of this study was to systematically evaluate the pelletization process parameters of kappa-carrageenan-containing formulations. The study dealt with the effect of 4 process parameters--screw speed, number of die holes, friction plate speed, and spheronizer temperature--on the pellet properties of shape, size, size distribution, tensile strength, and drug release. These parameters were varied systematically in a 2(4) full factorial design. In addition, 4 drugs--phenacetin, chloramphenicol, dimenhydrinate, and lidocaine hydrochloride--were investigated under constant process conditions. The most spherical pellets were achieved in a high yield by using a large number of die holes and a high spheronizer speed. There was no relevant influence of the investigated process parameters on the size distribution, mechanical stability, and drug release. The poorly soluble drugs, phenacetin and chloramphenicol, resulted in pellets with adequate shape, size, and tensile strength and a fast drug release. The salts of dimenhydrinate and lidocaine affected pellet shape, mechanical stability, and the drug release properties using an aqueous solution of pH 3 as a granulation liquid. In the case of dimenhydrinate, this was attributed to the ionic interactions with kappa-carrageenan, resulting in a stable matrix during dissolution that did not disintegrate. The effect of lidocaine is comparable to the effect of sodium ions, which suppress the gelling of carrageenan, resulting in pellets with fast disintegration and drug release characteristics. The pellet properties are affected by the process parameters and the active pharmaceutical ingredient used.     

Statistical evaluation of influence of viscosity and content of polymer on dipyridamole release from floating matrix tablets: A technical note

Conclusion  The present investigation described the influence of viscosity and content of HPMC on dipyridamole release using 3² full factorial design. All formulations had desired floating lag time (<2 minutes) regardless of viscosity and content of polymeric matrices. Results of multiple regression analysis indicate that both factors significantly affect the diffusion exponent (n), release rate constant (k), and percentage drug release at 1 hour, 4 hours, 6 hours, and 12 hour, (P<.05). Mechanism of drug release was found to be anomalous type to case-II transport depending upon the viscosity and content of polymer. It was found that content of HPMC had a dominant role in the initial phase of drug release, while in the later phase viscosity of HPMC Predominated. Published: August 24, 2007     

Assessment of the Influence Factors on Nasal Spray Droplet Velocity Using Phase-Doppler Anemometry (PDA)

Droplet velocity is an important parameter that can be used to characterize nasal spray products. In this study, a phase-Doppler anemometry (PDA) system was used to measure the droplet velocities of nasal sprays. A survey of seven commercial nasal spray products showed a range of droplet velocities from 6.7 to 19.2 m/s, all significantly different from each other. A three-level, four-factor Box–Behnken design of experiments (DOE) methodology were applied to investigate the influences of actuation parameters and formulation properties on nasal spray droplet velocity using a set of placebo formulations. The DOE study shows that all four input factors (stroke length, actuation velocity, concentration of the gelling agent, and concentration of the surfactant) have significant influence on droplet velocity. An optimized quadratic model generated from the DOE results describes the inherent relationships between the input factors and droplet velocity thus providing a better understanding of the input factor influences. Overall, PDA provides a new in vitro characterization method for the evaluation of inhalation drugs through assessment of spray velocity and may assist in product development to meet drug delivery equivalency requirements.     

Characterization of 5-fluorouracil microspheres for colonic delivery

The purpose of this investigation was to prepare and evaluate the colon-specific microspheres of 5-fluorouracil for the treatment of colon cancer. Core microspheres of alginate were prepared by the modified emulsification method in liquid paraffin and by cross-linking with calcium chloride. The core microspheres were coated with Eudragit S-100 by the solvent evaporation technique to prevent drug release in the stomach and small intestine. The microspheres were characterized by shape, size, surface morphology, size distribution, incorporation efficiency, and in vitro drug release studies. The outer surfaces of the core and coated microspheres, which were spherical in shape, were rough and smooth, respectively. The size of the core microspheres ranged from 22 to 55 μm, and the size of the coated microspheres ranged from 103 to 185 μm. The core microspheres sustained the drug release for 10 hours. The release studies of coated microspheres were performed in a pH progression medium mimicking the conditions of the gastrointestinal tract. Release was sustained for up to 20 hours in formulations with core microspheres to a Eudragit S-100 coat ratio of 1∶7, and there were no changes in the size, shape, drug content, differential scanning calorimetry thermogram, and in vitro drug release after storage at 40°C/75% relative humidity for 6 months.     

Sorbitan ester niosomes for topical delivery of rofecoxib

The aim of the present investigation is to encapsulate rofecoxib in niosomes and incorporate the prepared niosomes into dermal gel base for sustained therapeutic action. Niosomes were prepared by lipid film hydration technique and were analyzed for size, entrapment efficiency and drug retention capacity. Niosomal vesicles were then incorporated into blank carbopol gel to form niosomal gel. The in vitro permeation study across pig skin was performed using Keshary-Chien glass diffusion cell. The size and entrapment efficiency of the niosomal vesicles increased with gradual increase in HLB value of nonionic surfactants used. Maximum drug entrapment was observed with Span 20 with HLB value of 8.6 and drug leakage from vesicles was less at refrigerated condition than at the room temperature. Higher proportion of cholesterol made the niosomal formulation more stable with high drug retention properties. The niosomal gel showed a prolong drug release behavior compared to plain drug gel. Differential scanning calorimetric study of drug loaded gel and pig skin after permeation study confirmed inertness of carbopol gel base toward rofecoxib and absence of drug metabolism in the skin during permeation study, respectively. The niosomal formulations were successfully prepared by lipid film hydration technique using cholesterol and Span as nonionic surfactant. Presence of cholesterol made niosomes more stable with high drug entrapment efficiency and retention properties. The lower flux value of niosomal gel as compared to plain drug gel across pig skin assured the prolong drug release behavior with sustained action.