Sanjay Dey

Nanostructured Lipid Carriers (NLC)-Based Gel for the Topical Delivery of Aceclofenac: Preparation, Characterization, and In Vivo Evaluation.

The aim of this study was to prepare nanostructured lipid carriers (NLC)-based topical gel of aceclofenac for the treatment of inflammation and allied conditions. Stearic acid as the solid lipid, oleic acid as the liquid lipid, pluronic F68 as the surfactant, and phospholipon 90G as the co-surfactant were used. NLCs were prepared by melt-emulsification, low-temperature solidification, and high-speed homogenization methods. Characterization of the NLC dispersion was carried out through particle size analysis, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and an in vitro release study. The anti-inflammatory effect of the NLC gel was assessed by the rat paw edema technique and compared to marketed aceclofenac gel. The NLC dispersions exhibited d90% between 233 nm and 286 nm. All of the NLC showed high entrapment efficiency ranging from 67% to 82%. The particle size of NLC was further confirmed by the SEM study. The result of DSC showed that aceclofenac was dispersed in NLC in an amorphous state. Both the entrapment and release rate were affected by the percentage of oleic acid, but the method of preparation affected only the entrapment efficiency. The nanoparticulate dispersion was suitably gelled and assessed for in vitro permeation. Finally, NLC-based gels were found to possess superior (almost double) the anti-inflammatory activity compared to the marketed product. The anti-inflammatory activity of NLC gel showed a rapid onset of action, as well as a prolonged duration of action as compared with the marketed gel.

Topical delivery of aceclofenac as nanoemulsion comprising excipients having optimum emulsification capabilities: preparation, characterization and in vivo evaluation

Objective: The aim of the present study was to investigate the potential of a nanoemulsion for topical delivery of aceclofenac using different excipients having optimum emulsifying ability rather than their solubilizing capacity. Methods: The oil-in-water nanoemulsions were prepared by screening the excipients from the nanoemulsion region of pseudoternary phase diagram. The prepared nanoemulsions were subjected to different thermodynamic stability tests. The nanoemulsion formulations that passed thermodynamic stability tests were characterized for viscosity, droplet size, transmission electron microscopy, refractive index and in vitro skin permeation. The in vitro skin permeation profile of optimized nanoemulsion formulation (NE31, containing 23.85% Polyoxy-35-castor oil, 7.95% PEG 400 and 13.6% Triacetin) was compared with that of nanoemulsion gel (NG31) and marketed gel formulation (HIFENAC GEL (HIG)). In vivo anti-inflammatory efficacy studies were also carried out for NE31, NG31 and HIG. Results: The significant (p < 0.001) increase in in vitro permeability and in vivo anti-inflammatory efficacy of the NG31 formulation was observed as compared with HIG formulation. Conclusion: It can be concluded that the selection of surfactant and cosurfactant on the basis of their emulsification capabilities other than the solubilizing capacity of drug is an important criterion for the formulation of nanoemulsion.

Floating capsules containing alginate-based beads of salbutamol sulfate: In vitro-in vivo evaluations.

The present study deals with the development and evaluations of stomach-specific floating capsules containing salbutamol sulfate-loaded oil-entrapped alginate-based beads. Salbutamol sulfate-loaded oil-entrapped beads were prepared and capsulated within hard gelatin capsules (size 1). The effects of HPMC K4M and potato starch weight masses on drug encapsulation efficiency (DEE) of beads and cumulative drug release at 10h (R10 h) from capsules was analyzed by 3(2) factorial design. The optimization results indicate increasing of DEE in the oil-entrapped beads and decreasing R10 h from capsules with increment of HPMC K4M and potato starch weight masses. The optimized formulation showed DEE of 70.02 ± 3.16% and R10 h of 56.96 ± 2.92%. These capsules showed floatation over 6h and sustained drug release over 10h in gastric pH (1.2). In vivo X-ray imaging study of optimized floating capsules in rabbits showed stomach-specific gastroretention over a prolonged period.

Formulation development and optimization of bilayer tablets of aceclofenac

Objective: The objective of the present study was to develop bilayer tablets of aceclofenac that are characterized by initial burst drug release followed by sustained release of drug. Methods: The fast-release layer of the bilayer tablet was formulated using microcrystaline cellulose (MCC) and HPMC K4M. The amount of HPMC E4M (X1) and MCC (X2) was used as independent variables for optimization of sustained release formulation applying 32 factorial design. Three dependent variables were considered: percentage of aceclofenac release at 1 h, percentage of aceclofenac release at 12 h, and time to release 50% of drug (t50%). The composition of optimum formulation of sustained release tablets were employed to formulate double layer tablets. Results: The results indicate that X1 and X2 significantly affected the release properties of aceclofenac from sustained release formulation. The double layer tablets containing fast-release layer showed an initial burst drug release of more than 30% of its drug content during first 1 h followed by sustained release of the drug for a period of 24 h. Conclusion: The double layer tablets for aceclofenac can be successfully employed as once-a-day oral-controlled release drug delivery system characterized by initial burst release of aceclofenac for providing the loading dose of drug.

Polymers derived from Xanthomonas campesteris and Cyamopsis tetragonolobus used as retardant materials for the formulation of sustained release floating matrix tablet of atenolol

The objective of the present study was to develop, optimize, in vitro, and in vivo evaluation of floating matrix tablet of atenolol using polymer blend derived from Xanthomonas campesteris and Cyamopsis tetragonolobus that are characterized by release requirements of sustained-release product and to improve the oral bioavailability of the drug. A 3(2) full factorial design was employed to optimize the tablets, where content of polymer blend (X1) and ratio of xanthan gum-to-guar gum (X2) were considered as independent variables. The effects of independent variables on dependent variables, i.e. floating time, diffusion exponent, and time to release 50% of atenolol were evaluated. The in vivo pharmacokinetic parameters of the optimized formulation were compared with the marketed sustained release formulation of atenolol (Aten(®)). The optimized formulation containing 20% (w/w) of polymer blend and 50:50 ratio of xanthan gum-to-guar gum was able to float more than 12h and showed the desired sustained drug release from the tablets. In vivo retention studies in rabbit stomach showed the gastric residence of tablet up to 6h. The in vivo study of optimized tablets illustrated significant improvement in the oral bioavailability of atenolol in rabbits. It can be concluded that floating matrix tablet of atenolol prepared by using xanthan gum and guar gum has potential for sustained release of the drug as well as improved oral bioavailability through enhanced gastric residence time of formulation in stomach.

Formulation and Evaluation of Fixed-Dose Combination of Bilayer Gastroretentive Matrix Tablet Containing Atorvastatin as Fast-Release and Atenolol as Sustained-Release

The objective of the present study was to develop bilayer tablets of atorvastatin and atenolol that are characterized by initial fast-release of atorvastatin in the stomach and comply with the release requirements of sustained-release of atenolol. An amorphous, solvent evaporation inclusion complex of atorvastatin with β-cyclodextrin, present in 1 : 3 (drug/cyclodextrin) molar ratio, was employed in the fast-release layer to enhance the dissolution of atorvastatin. Xanthan gum and guar gum were integrated in the sustained-release layer. Bilayer tablets composed of sustained-release layer (10% w/w of xanthan gum and guar gum) and fast-release layer [1 : 3 (drug/cyclodextrin)] showed the desired release profile. The atorvastatin contained in the fast-release layer showed an initial fast-release of more than 60% of its drug content within 2 h, followed by sustained release of the atenolol for a period of 12 h. The pharmacokinetic study illustrated that the fast absorption and increased oral bioavailability of atorvastatin as well as therapeutic concentration of atenolol in blood were made available through adoption of formulation strategy of bilayer tablets. It can be concluded that the bilayer tablets of atorvastatin and atenolol can be successfully employed for the treatment of hypertension and hypercholesterolemia together through oral administration of single tablet.

Enhanced Percutaneous Permeability of Acyclovir by DMSO from Topical Gel Formulation

The aim of this study was to investigate the effect of DMSO on the permeation of acyclovir in the form of topical gel formulations. Different formulations were prepared containing carbopol 934P, acyclovir (1 % w/w) and selected concentration of DMSO (0 to 10% w/w) to evaluate drug content, spreadibility, pH, viscosity, and in-vitro permeation through mouse epidermis and porcine skin. FTIR spectrometry was used to investigate physical state of drug in the gel formulations. The mechanisms of drug permeation were evaluated by FTIR spectrophotometer and histopathological studies. The carbopol 934P gel was found to contain 95.62 to 98.89 % of acyclovir and spreadibility was found in the range of 10.75 to 11.75 g.cm/sec. The pH of all formulations was found near to the skin pH value. The viscosity of the formulations was found inversely proportional with drug permeation. A maximum permeation flux of acyclovir (463.42±36.41μg/cm2.h) through porcine skin was observed with an enhancement ratio of 1.55, when DMSO was incorporated at a concentration of 10%w/w in gel system. The FTIR spectra revealed the absence of drug-polymer interaction. From FTIR spectroscopy and histopathological studies it was evident that the permeation of acyclovir, across mouse and porcine skin, were increased in presence of DMSO which can be attributed to the partial extraction of lipids in the stratum corneum. The results suggest that DMSO may be useful for enhancing the skin permeability of acyclovir from transdermal therapeutic system containing carbopol 934P gel as reservoir

Three Levels Face Centered Central Composite Design of Colon Targeted Micro-Particulates System of Celecoxib: Screening of Formulations Variables and in vivo Studies

Celecoxib is a well known non-steroidal anti-inflammatory drug (NSAID) and extensively employed for the treatment of arthritis. The aim of the present study was to design, develop and optimization of micro particulates system, for colon specific delivery of celecoxib for both local (in prophylaxis of colorectal adreno-carcinoma) and systemic (in chrono-therapeutic treatment of arthritis) therapy. The aim of the present work was to elucidate the effect of formulation variables e.g., amount of eudragit polymer (X1), surfactant concentration (X2) and agitation speed (X3) on in-vitro release profiles (Y1-Y3), drug entrapment efficiency (Y4) and particle size (Y5) of micro-particulates system of celecoxib. Microspheres were formulated with the combination of ethyl cellulose (EC) and eudragit RS100/eudragit S100; by using a novel quasi emulsion solvent diffusion technique. Developed formulations were characterized and evaluated on the basis of FTIR, thermal, particle size, SEM and XRD analysis. The formulation variables were optimized by response surface methodology (RSM). Best optimized delayed release formulation was further subjected to the in vivo x-ray studies to evaluate the site specificity. It was found that in-vitro release (Y1-Y3) decreased significantly (p<0.05) with increase in amount of eudragit polymer but increased significantly (p<0.05) with an increase in surfactant concentration and stirring speed. FTIR study indicated that no strong chemical interaction took place between the drug and excipients of prepared formulations. DSC and XRD studies indicated that drug was present in the amorphous state. The X-ray photographs revealed that the swelling layer eroded from the outer surface and a size reduction was seen after 6 hrs when optimized microspheres reached the site of colon. Therefore, this approach suggested that the combination of eudragit S100 and ethyl cellulose microspheres may be useful for the delivery of maximum amount of celecoxib in intact form to the colon.

Transdermal Lipid Nanocarriers: A Potential Delivery System for Lornoxicam.

BACKGROUND Lornoxicam, is a NSAID of the oxicam class. Its short duration of action owing to rapid elimination and gastrointestinal side effects limits its usefulness when administered orally. OBJECTIVE The primary objective of the proposed work is to develop suitable lipid nanocarriers for transdermal delivery of Lornoxicam with increased drug residence time at local site of inflamation and in systemic circulation, overcoming undesired gastrointestinal side effects. METHOD Lornoxicam loaded lipid nanocarriers like solid lipid nanocarriers (SLN), nano-structured lipid carriers (NLC) & nanoemulsions (NE) were prepared by high-speed homogenization technique. RESULT The particle size, zeta potential, and polydispersity index as obtained, were in the range of 140- 193 nm, -22 to -32 mV, and 0.354-0.301 for SLN formulations and 146-201 nm, -23 to -30 mV, and 0.355-0.354 for NLC formulations respectively. Characterization of stable NE revealed that globule size, zeta potential and polydispersity index were within the range of 138 to 195 nm, -26.1±0.123 mV and 0.195 ± 1.231 respectively. It was also observed that entrapment efficacy and drug loading improved as the lipid concentration was increased. The results obtained from the in vitro permeation study and in vivo anti-inflammatory study showed controlled drug permeation, increased bioavailability, longer retention and better therapeutic potential of Lornoxicam after transdermal application of lipid nanoparticles as compared to conventional gel. CONCLUSION It can be concluded that the developed lipid nanoparticle loaded gel was found to be a suitable drug delivery carrier for transdermal delivery of Lornoxicam to increase the residence time of drug in systemic circulation and to combat the gastrointestinal side effects.

Lipid nanoparticles for topical application of drugs for skin diseases

The topical route for drug administration has acquired appraisal due to the large surface area of the skin and the controlled manner of drug delivery results in the reduction of systemic adverse effects. Moreover, this route of drug administration is advantageous mainly in the cases where oral delivery of drugs become cumbersome. This chapter first explains the structure and properties of the skin which further helps the reader to understand the following topics. The merits and demerits have been highlighted by the authors for a better understanding of the system. The chapter throws light on the different lipid nanocarriers for tropical drug-delivery such as Solid Lipid Nanoparticles, Nanostructured Lipid Carriers, Liposomes, Ethosomes, Microemulsions and Lipid Nanocapsules. The potential mechanisms of action for the topical delivery of these devices are elaborated accordingly. The chapter has been concluded with different pharmaceutical formulations and its benefits.