Drug delivery to the brain has remained a significant challenge in treating neurodegenerative dis... more Drug delivery to the brain has remained a significant challenge in treating neurodegenerative disorders such as Alzheimer's disease due to the presence of the blood-brain barrier, which primarily obstructs the access of drugs and biomolecules into the brain. Several methods to overcome the blood-brain barrier have been employed, such as chemical disruption, surgical intervention, focused ultrasound, intranasal delivery and using nanocarriers. Nanocarrier systems remain the method of choice and have shown promising results over the past decade to achieve better drug targeting. Polymeric nanocarriers and lipidic nanoparticles act as a carrier system providing better encapsulation of drugs, site-specific delivery, increased bioavailability and sustained release of drugs. The surface modifications and functionalization of these nanocarrier systems have greatly facilitated targeted drug delivery. The safety and efficacy of these nanocarrier systems have been ascertained by several in...
Contact lenses are widely used for ophthalmic drug delivery, but incorporation of drug or formula... more Contact lenses are widely used for ophthalmic drug delivery, but incorporation of drug or formulation in the contact lenses affects its optical and physical property. In the present study, we have designed a novel hyaluronic acid (HA)-laden ring implant contact lenses (modified cast moulding method), to circumvent the changes in critical lens property. The objective was to improve the ocular residence time of HA, by providing sustained ocular HA delivery through implant contact lenses for the treatment of dry eye syndrome. Optimization of HA-implant was carried out using 3(2) factorial design by tailoring the amount of cross linker and thickness of implant, to achieve sustained HA release with constraint on effective ion diffusivity. The in vivo pharmacokinetic study in rabbit tear fluid showed sustained HA release up to 15days, by fabricating implant (80μgHA loading) with 78.4μm thickness (total thickness of lens=100μm) using 0.925% of cross linker, with effective ion diffusivity&g...
Ramipril, potent anti-hypertensive agent has been used in the treatment of hypertensive disorders... more Ramipril, potent anti-hypertensive agent has been used in the treatment of hypertensive disorders. It has low bioavailability of 28-35% and short biological half-life (i.e. 2-4 hr). Thus this study attempts to evaluate chitosan-alginate nanoparticles as a novel drug delivery for Ramipril to sustain drug release and improve oral bioavailability. Nanoparticles were prepared by ionotropic pre-gelation technique using chitosan and sodium alginate polymers. Total nine formulations (F1 to F9) were prepared by varying the polymer concentrations. The nanoparticles were characterized for particle size, drug content, drug entrapment efficiency, zeta potential, surface morphology (TEM), percentage yield, in-vitro diffusion study, in-vivo bioavailability studies and stability studies. All prepared formulations were in the nanosize range of 190.5±6.15nm to 361.76±3.32 and with spherical morphology. The drug content and entrapment efficiency was found to maximum for F5 formulation, percentage yield was in the range of 53.72±2.04 to 77.91±0.565% which mainly depends upon polymer concentration. The zeta potential of optimised formulation F5 was found to be-34.2mV, showed good stability of nanoparticles during storage. The in-vitro drug release profile showed the suitability of nanoparticles for pH dependent and sustained release of Ramipril for prolonged time. Kinetic modelling revealed that the in-vitro drug release followed peppas model and non-fickian diffusion. From the in vivo studies it was predicted that oral bioavailability of Ramipril nanoparticles improved 2.17 times more than the pure drug. Stability studies carried out for optimized formulation F5 showed that the nanoparticles are more stable at 5±3°C.
Presently, the most common method for in-vivo imaging of Dry Powder formulations of salbutamol is... more Presently, the most common method for in-vivo imaging of Dry Powder formulations of salbutamol is adsorption of 99mTc DTPA over the particles. The major problem with this method is that it is based on physical adsorption of dry radioactivity on the particle. One can never be sure that the radioactivity has not disassociated in vivo and whether the radioactivity distribution in the respiratory tree in fact represents true drug distribution. We recently developed the technology to chemically label the drug particles with 99mTc without changing their size characteristics. AIM: To develop nanosized particles of salbutamol sulphate (SBM), to label the pre-formed particles and to image their distribution in the human respiratory tree. This information will be of immense help to clinicians to predict response of patients to salbutamol DPI. MATERIALS & METHODS: Salbutamol sulphate was dispersed in a solvent by antisolvent precipitation technique to form a nanosuspension. Dry nano-particles ...
Recent Patents on Drug Delivery & Formulation, 2008
Microemulsions represent a promising carrier system for cosmetic active ingredients due to their ... more Microemulsions represent a promising carrier system for cosmetic active ingredients due to their numerous advantages over the existing conventional formulations. They are capable of solubilizing both hydrophilic and lipophilic ingredients with relatively higher encapsulation. There is growing recognition of their potential benefits in the field of cosmetic science in addition to the drug delivery. They are now being widely investigated for preparing personal care products with superior features such as having improved product efficiency, stability or appearance. They are well suited for the preparation of various cosmetic products for use as moisturizing and soothing agents, as sunscreens, as antiperspirants and as body cleansing agents. They are also valuable for use in hair care compositions which ensure a good conditioning of the hair as well as good hair feel and hair gloss. They have also found application in after shave formulations which upon application to the skin provide reduced stinging and irritation and a comforting effect without tackiness. These newer formulations elicit very good cosmetic attributes and high hydration properties with rapid cutaneous penetration which may accentuate their role in topical products. These smart systems are also suitable for perfuming purposes where minimum amount of organic solvents is required, such as for perfuming skin or hair. This article highlights the recent innovations in the field of microemulsion technology as claimed by different patents which can bring unique products with great commercial prospects in a very competitive and lucrative global cosmetic market.
Recent Patents on Drug Delivery & Formulation, 2008
Microemulsions are isotropic, thermodynamically stable transparent (or translucent) systems of oi... more Microemulsions are isotropic, thermodynamically stable transparent (or translucent) systems of oil, water and surfactant, frequently in combination with a cosurfactant with a droplet size usually in the range of 20-200 nm. They can be classified as oil-in-water (o/w), water-in-oil (w/o) or bicontinuous systems depending on their structure and are characterized by ultra low interfacial tension between oil and water phases. These versatile systems are currently of great technological and scientific interest to the researchers because of their potential to incorporate a wide range of drug molecules (hydrophilic and hydrophobic) due to the presence of both lipophilic and hydrophilic domains. These adaptable delivery systems provide protection against oxidation, enzymatic hydrolysis and improve the solubilization of lipophilic drugs and hence enhance their bioavailability. In addition to oral and intravenous delivery, they are amenable for sustained and targeted delivery through ophthalmic, dental, pulmonary, vaginal and topical routes. Microemulsions are experiencing a very active development as reflected by the numerous publications and patents being granted on these systems. They have been used to improve the oral bioavailability of various poorly soluble drugs including cyclosporine and paclitaxel as professed by Hauer et al., US patent 7235248, and Gao et al., US patent 7115565, respectively. Furthermore, they can be employed for challenging tasks such as carrying chemotherapeutic agents to neoplastic cells and oral delivery of insulin as diligently described by Maranhao, US patent 5578583 and Burnside et al., US patent 5824638 respectively. The recent commercial success of Sandimmune Neoral ® (Cyclosporine A), Fortovase ® (Saquinavir), Norvir ® (Ritonavir), etc. also reflects the tremendous potential of these newer drug therapeutic systems. A critical evaluation of recent patents claiming different approaches to improve the drug delivery is the focus of the current review.
Chitosan (CS) nanoparticles of thymoquinone (TQ) were prepared by the ionic gelation method and a... more Chitosan (CS) nanoparticles of thymoquinone (TQ) were prepared by the ionic gelation method and are characterized on the basis of surface morphology, in vitro or ex vivo release, dynamic light scattering, and X-ray diffractometry (XRD) studies. Dynamic laser light scattering and transmission electron microscopy confirmed the particle diameter was between 150 to 200 nm. The results showed that the particle size of the formulation was significantly affected by the drug:CS ratio, whereas it was least significantly affected by the tripolyphosphate:CS ratio. The entrapment efficiency and loading capacity of TQ was found to be 63.3% ± 3.5% and 31.23% ± 3.14%, respectively. The drug-entrapment efficiency and drug-loading capacity of the nanoparticles appears to be inversely proportional to the drug:CS ratio. An XRD study proves that TQ dispersed in the nanoparticles changes its form from crystalline to amorphous. This was further confirmed by differential scanning calorimetry thermography....
The precipitation technique was used to prepare non-polymeric alendronate nanoparticles. The infl... more The precipitation technique was used to prepare non-polymeric alendronate nanoparticles. The influence of various formulation parameters on the average particle size was investigated and the effect of various stabilizers (PVA, tween, chitosan, alginate, PEG, HPMC, poloxomers) was evaluated. The selection of surfactant was a key factor to produce particles with desired properties. Poloxomer F68 was found best in achieving the minimum particle size and providing physical stability to the drug. On basis of preliminary trials, a central composite design was employed to study the effect of independent variables, drug concentration (X 1 ), antisolvent volume (X 2 ), stirring speed (X 3 ), and stabilizer concentration (X 4 ) on the average particle size. The drug and stabilizer concentrations exhibited a more significant effect on a dependent variable. The particle size varied from 62 to 803.3 nm depending upon the significant terms. The validation of optimization study, performed using six confirmatory runs, indicated very high degree of prognostic ability of response surface methodology, with mean percentage error (AESD) as À2.32 AE 2.47. The minimum particle size (44.11 nm) was predicted at 10 mg/ml drug concentration, 20 ml antisolvent volume, 925 rpm stirring speed, and 8.5% stabilizer concentration with 98.16% experimental validity. Respirable fraction for optimized nanosized alendronate (43.85% AE 0.52%) was significantly higher when compared with commercial alendronate (17.6 AE 0.32). Mass median aerodynamic diameter of designed particles was 3.45 mm with geometric standard deviation of 2.10.
Ganciclovir (GCV) plays an important role in the treatment of ocular viral infections. A high dos... more Ganciclovir (GCV) plays an important role in the treatment of ocular viral infections. A high dose results in dose-related toxicity including bone marrow suppression and neutropenia. The aim of the present study was to investigate the comparative potential of different mucoadhesive nano formulations for the topical ocular delivery of Ganciclovir. GCV mucoadhesive Nanoemulsions (GCV-NEs), chitosan nanoparticles (GCV-NPs), GCV mucoadhesive niosomal dispersion (GCV-NDs) were prepared by the reverse-phase evaporation technique. All of the three formulations were evenly round in shape with mean particle size in the range of 23-200 nm. These results indicated the nonirritant and nontoxic nature of the developed formulations. The achieved results may be useful for formulation development of GCV, which could be effective in the treatment of ocular infections by topical instillation.
Encapsulation of Ganciclovir in lipophilic vesicular structure may be expected to enhance the ora... more Encapsulation of Ganciclovir in lipophilic vesicular structure may be expected to enhance the oral absorption and prolong the existence of the drug in the systemic circulation. So the purpose of the present study was to improve the oral bioavailability of Ganciclovir by preparing nanosized niosomal dispersion. Niosomes were prepared from Span40, Span60, and Cholesterol in the molar ratio of 1:1, 2:1, 3:1, and 3:2 using reverse evaporation method. The developed niosomal dispersions were characterized for entrapment efficiency, size, shape, in vitro drug release, release kinetic study, and in vivo performance. Optimized formulation (NG8; Span60:Cholesterol 3:2 molar ratio) has shown a significantly high encapsulation of Ganciclovir (89±2.13%) with vesicle size of 144±3.47 nm (polydispersity index [PDI]=0.08). The in vitro release study signifies sustained release profile of niosomal dispersions. Release profile of prepared formulations have shown that more than 85.2±0.015% drug was released in 24 h with zero-order release kinetics. The results obtained also revealed that the types of surfactant and Cholesterol content ratio altered the entrapment efficiency, size, and drug release rate from niosomes. In vivo study on rats reveals five-time increment in bioavailability of Ganciclovir after oral administration of optimized formulation (NG8) as compared with tablet. The effective drug concentration (>0.69 µg/mL in plasma) was also maintained for at least 8 h on administration of the niosomal formulation. In conclusion, niosomes can be proposed as a potential oral delivery system for the effective delivery of Ganciclovir.
Microemulsions are isotropic, thermodynamically stable transparent (or translucent) systems of oi... more Microemulsions are isotropic, thermodynamically stable transparent (or translucent) systems of oil, water, and surfactant, frequently in combination with a cosurfactant with a droplet size usually in the range of 20-200 nm. Since their discovery, they have attained increasing significance both in basic research and in industry. Due to their distinct advantages such as enhanced drug solubility, thermodynamic stability, facile preparation, and low cost, uses and applications of microemulsions have been numerous. Recently, there is a surge in the exploration of microemulsion for transdermal drug delivery for their ability to incorporate both hydrophilic (5-fluorouracil, apomorphine hydrochloride, diphenhydramine hydrochloride, tetracaine hydrochloride, and methotrexate) and lipophilic drugs (estradiol, finasteride, ketoprofen, meloxicam, felodipine, and triptolide) and enhance their permeation. Very low surface tension in conjunction with enormous increase in the interfacial area due to nanosized droplets of the microemulsion influences the drug permeation across the skin. A large number of oils and surfactants are available, which can be used as components of microemulsion systems for transdermal delivery but their toxicity, irritation potential, and unclear mechanism of action limit their use. Besides surfactants, oils can also act as penetration enhancers (oleic acid, linoleic acid, isopropyl myristate, isopropyl palmitate, etc.). The transdermal drug delivery potential of microemulsions is dependent not only on the applied constituents of the vehicle but also drastically on the composition/internal structure of the phases which may promote or hamper the drug distribution in the vehicles. This article explores microemulsion as transdermal drug delivery vehicles with emphasis on components selection for enhanced drug permeation and skin tolerability of these systems and further future directions.
The aim of the present study was to investigate the nanoemulsion system for enhanced percutaneous... more The aim of the present study was to investigate the nanoemulsion system for enhanced percutaneous penetration of domperidone. Pseudoternary phase diagrams were constructed in order to optimize the surfactant, cosurfactant and surfactant: cosurfactant weight ratios (Smix). Nine nanoemulsion formulations were selected, characterized and their ex-vivo permeation studies using rat skin were performed. The nanoemulsion formulations had small droplet size (<90 nm), uniform size distribution (PI, < 0.2) and low viscosity (<160 mP). The results demonstrated that the droplet size and viscosity of nanoemulsion decreased following decrease in the concentration of polysorbate 20, whereas transdermal flux was increased. The optimized formulation NE-B1, which contained oleic acid (4 % w/w), polysorbate 20 (10 % w/w), diethylene glycol monoethyl ether (20 % w/w) and water (64 % w/w) showed significant increase (P < 0.01) in the transdermal flux (169.32 ± 8.33 g.h -1 cm -2 ). The in vivo studies revealed a 3.5 fold increase in relative bioavailability through transdermal application of NE-B1 formulation compared to oral drug suspension. Moreover, the effective drug plasma concentration was maintained for 16 hour after the transdermal application indicated that the developed nanoemulsion systems could be a promising carrier for the transdermal delivery of domperidone for prolonged period.
Paracetamol is a sparingly soluble bitter tasting drug. It is widely used as an analgesic and ant... more Paracetamol is a sparingly soluble bitter tasting drug. It is widely used as an analgesic and antipyretic. Complexation of drug with different cyclodextrins (α, β and HP-β-CD) was attempted to improve solubility of Paracetamol. During the drug excipient interaction studies, α, β cyclodextrins elicited analytical interference and showed considerable absorbance at λmax (243.5 nm) of Paracetamol while the ones constituting of hydroxypropyl-beta-cyclodextrin (HP-β-CD) did not show any such interference. Therefore, the present study is concentrated on exploring HP-β-CD as complexing agent. Phase solubility studies showed that complexation of Paracetamol/HP-β-CD at molar ratio 1:1 and showed A L type solubility curve. Complexation was done by various methods like physical mixing, kneading and freeze drying and resulting drug complexes were characterized by Differential Scanning Calorimetry (DSC) and Fourier Transform Infrared Spectroscopy (FTIR). The thermograms obtained showed an endothermic peak for Paracetamol, for physical mixture to some extent for kneaded mixture, but was completely eliminated for freeze dried product (Inclusion complex). Similar results were obtained during IR studies. Therefore, solid inclusion complex of paracetamol prepared by freeze drying method was found to be an ideal complex. The solubility of paracetamol, was significantly increased (six folds of normal solubility) by complexation with HP-β-CD.
Drug delivery to the brain has remained a significant challenge in treating neurodegenerative dis... more Drug delivery to the brain has remained a significant challenge in treating neurodegenerative disorders such as Alzheimer's disease due to the presence of the blood-brain barrier, which primarily obstructs the access of drugs and biomolecules into the brain. Several methods to overcome the blood-brain barrier have been employed, such as chemical disruption, surgical intervention, focused ultrasound, intranasal delivery and using nanocarriers. Nanocarrier systems remain the method of choice and have shown promising results over the past decade to achieve better drug targeting. Polymeric nanocarriers and lipidic nanoparticles act as a carrier system providing better encapsulation of drugs, site-specific delivery, increased bioavailability and sustained release of drugs. The surface modifications and functionalization of these nanocarrier systems have greatly facilitated targeted drug delivery. The safety and efficacy of these nanocarrier systems have been ascertained by several in...
Contact lenses are widely used for ophthalmic drug delivery, but incorporation of drug or formula... more Contact lenses are widely used for ophthalmic drug delivery, but incorporation of drug or formulation in the contact lenses affects its optical and physical property. In the present study, we have designed a novel hyaluronic acid (HA)-laden ring implant contact lenses (modified cast moulding method), to circumvent the changes in critical lens property. The objective was to improve the ocular residence time of HA, by providing sustained ocular HA delivery through implant contact lenses for the treatment of dry eye syndrome. Optimization of HA-implant was carried out using 3(2) factorial design by tailoring the amount of cross linker and thickness of implant, to achieve sustained HA release with constraint on effective ion diffusivity. The in vivo pharmacokinetic study in rabbit tear fluid showed sustained HA release up to 15days, by fabricating implant (80μgHA loading) with 78.4μm thickness (total thickness of lens=100μm) using 0.925% of cross linker, with effective ion diffusivity&g...
Ramipril, potent anti-hypertensive agent has been used in the treatment of hypertensive disorders... more Ramipril, potent anti-hypertensive agent has been used in the treatment of hypertensive disorders. It has low bioavailability of 28-35% and short biological half-life (i.e. 2-4 hr). Thus this study attempts to evaluate chitosan-alginate nanoparticles as a novel drug delivery for Ramipril to sustain drug release and improve oral bioavailability. Nanoparticles were prepared by ionotropic pre-gelation technique using chitosan and sodium alginate polymers. Total nine formulations (F1 to F9) were prepared by varying the polymer concentrations. The nanoparticles were characterized for particle size, drug content, drug entrapment efficiency, zeta potential, surface morphology (TEM), percentage yield, in-vitro diffusion study, in-vivo bioavailability studies and stability studies. All prepared formulations were in the nanosize range of 190.5±6.15nm to 361.76±3.32 and with spherical morphology. The drug content and entrapment efficiency was found to maximum for F5 formulation, percentage yield was in the range of 53.72±2.04 to 77.91±0.565% which mainly depends upon polymer concentration. The zeta potential of optimised formulation F5 was found to be-34.2mV, showed good stability of nanoparticles during storage. The in-vitro drug release profile showed the suitability of nanoparticles for pH dependent and sustained release of Ramipril for prolonged time. Kinetic modelling revealed that the in-vitro drug release followed peppas model and non-fickian diffusion. From the in vivo studies it was predicted that oral bioavailability of Ramipril nanoparticles improved 2.17 times more than the pure drug. Stability studies carried out for optimized formulation F5 showed that the nanoparticles are more stable at 5±3°C.
Presently, the most common method for in-vivo imaging of Dry Powder formulations of salbutamol is... more Presently, the most common method for in-vivo imaging of Dry Powder formulations of salbutamol is adsorption of 99mTc DTPA over the particles. The major problem with this method is that it is based on physical adsorption of dry radioactivity on the particle. One can never be sure that the radioactivity has not disassociated in vivo and whether the radioactivity distribution in the respiratory tree in fact represents true drug distribution. We recently developed the technology to chemically label the drug particles with 99mTc without changing their size characteristics. AIM: To develop nanosized particles of salbutamol sulphate (SBM), to label the pre-formed particles and to image their distribution in the human respiratory tree. This information will be of immense help to clinicians to predict response of patients to salbutamol DPI. MATERIALS & METHODS: Salbutamol sulphate was dispersed in a solvent by antisolvent precipitation technique to form a nanosuspension. Dry nano-particles ...
Recent Patents on Drug Delivery & Formulation, 2008
Microemulsions represent a promising carrier system for cosmetic active ingredients due to their ... more Microemulsions represent a promising carrier system for cosmetic active ingredients due to their numerous advantages over the existing conventional formulations. They are capable of solubilizing both hydrophilic and lipophilic ingredients with relatively higher encapsulation. There is growing recognition of their potential benefits in the field of cosmetic science in addition to the drug delivery. They are now being widely investigated for preparing personal care products with superior features such as having improved product efficiency, stability or appearance. They are well suited for the preparation of various cosmetic products for use as moisturizing and soothing agents, as sunscreens, as antiperspirants and as body cleansing agents. They are also valuable for use in hair care compositions which ensure a good conditioning of the hair as well as good hair feel and hair gloss. They have also found application in after shave formulations which upon application to the skin provide reduced stinging and irritation and a comforting effect without tackiness. These newer formulations elicit very good cosmetic attributes and high hydration properties with rapid cutaneous penetration which may accentuate their role in topical products. These smart systems are also suitable for perfuming purposes where minimum amount of organic solvents is required, such as for perfuming skin or hair. This article highlights the recent innovations in the field of microemulsion technology as claimed by different patents which can bring unique products with great commercial prospects in a very competitive and lucrative global cosmetic market.
Recent Patents on Drug Delivery & Formulation, 2008
Microemulsions are isotropic, thermodynamically stable transparent (or translucent) systems of oi... more Microemulsions are isotropic, thermodynamically stable transparent (or translucent) systems of oil, water and surfactant, frequently in combination with a cosurfactant with a droplet size usually in the range of 20-200 nm. They can be classified as oil-in-water (o/w), water-in-oil (w/o) or bicontinuous systems depending on their structure and are characterized by ultra low interfacial tension between oil and water phases. These versatile systems are currently of great technological and scientific interest to the researchers because of their potential to incorporate a wide range of drug molecules (hydrophilic and hydrophobic) due to the presence of both lipophilic and hydrophilic domains. These adaptable delivery systems provide protection against oxidation, enzymatic hydrolysis and improve the solubilization of lipophilic drugs and hence enhance their bioavailability. In addition to oral and intravenous delivery, they are amenable for sustained and targeted delivery through ophthalmic, dental, pulmonary, vaginal and topical routes. Microemulsions are experiencing a very active development as reflected by the numerous publications and patents being granted on these systems. They have been used to improve the oral bioavailability of various poorly soluble drugs including cyclosporine and paclitaxel as professed by Hauer et al., US patent 7235248, and Gao et al., US patent 7115565, respectively. Furthermore, they can be employed for challenging tasks such as carrying chemotherapeutic agents to neoplastic cells and oral delivery of insulin as diligently described by Maranhao, US patent 5578583 and Burnside et al., US patent 5824638 respectively. The recent commercial success of Sandimmune Neoral ® (Cyclosporine A), Fortovase ® (Saquinavir), Norvir ® (Ritonavir), etc. also reflects the tremendous potential of these newer drug therapeutic systems. A critical evaluation of recent patents claiming different approaches to improve the drug delivery is the focus of the current review.
Chitosan (CS) nanoparticles of thymoquinone (TQ) were prepared by the ionic gelation method and a... more Chitosan (CS) nanoparticles of thymoquinone (TQ) were prepared by the ionic gelation method and are characterized on the basis of surface morphology, in vitro or ex vivo release, dynamic light scattering, and X-ray diffractometry (XRD) studies. Dynamic laser light scattering and transmission electron microscopy confirmed the particle diameter was between 150 to 200 nm. The results showed that the particle size of the formulation was significantly affected by the drug:CS ratio, whereas it was least significantly affected by the tripolyphosphate:CS ratio. The entrapment efficiency and loading capacity of TQ was found to be 63.3% ± 3.5% and 31.23% ± 3.14%, respectively. The drug-entrapment efficiency and drug-loading capacity of the nanoparticles appears to be inversely proportional to the drug:CS ratio. An XRD study proves that TQ dispersed in the nanoparticles changes its form from crystalline to amorphous. This was further confirmed by differential scanning calorimetry thermography....
The precipitation technique was used to prepare non-polymeric alendronate nanoparticles. The infl... more The precipitation technique was used to prepare non-polymeric alendronate nanoparticles. The influence of various formulation parameters on the average particle size was investigated and the effect of various stabilizers (PVA, tween, chitosan, alginate, PEG, HPMC, poloxomers) was evaluated. The selection of surfactant was a key factor to produce particles with desired properties. Poloxomer F68 was found best in achieving the minimum particle size and providing physical stability to the drug. On basis of preliminary trials, a central composite design was employed to study the effect of independent variables, drug concentration (X 1 ), antisolvent volume (X 2 ), stirring speed (X 3 ), and stabilizer concentration (X 4 ) on the average particle size. The drug and stabilizer concentrations exhibited a more significant effect on a dependent variable. The particle size varied from 62 to 803.3 nm depending upon the significant terms. The validation of optimization study, performed using six confirmatory runs, indicated very high degree of prognostic ability of response surface methodology, with mean percentage error (AESD) as À2.32 AE 2.47. The minimum particle size (44.11 nm) was predicted at 10 mg/ml drug concentration, 20 ml antisolvent volume, 925 rpm stirring speed, and 8.5% stabilizer concentration with 98.16% experimental validity. Respirable fraction for optimized nanosized alendronate (43.85% AE 0.52%) was significantly higher when compared with commercial alendronate (17.6 AE 0.32). Mass median aerodynamic diameter of designed particles was 3.45 mm with geometric standard deviation of 2.10.
Ganciclovir (GCV) plays an important role in the treatment of ocular viral infections. A high dos... more Ganciclovir (GCV) plays an important role in the treatment of ocular viral infections. A high dose results in dose-related toxicity including bone marrow suppression and neutropenia. The aim of the present study was to investigate the comparative potential of different mucoadhesive nano formulations for the topical ocular delivery of Ganciclovir. GCV mucoadhesive Nanoemulsions (GCV-NEs), chitosan nanoparticles (GCV-NPs), GCV mucoadhesive niosomal dispersion (GCV-NDs) were prepared by the reverse-phase evaporation technique. All of the three formulations were evenly round in shape with mean particle size in the range of 23-200 nm. These results indicated the nonirritant and nontoxic nature of the developed formulations. The achieved results may be useful for formulation development of GCV, which could be effective in the treatment of ocular infections by topical instillation.
Encapsulation of Ganciclovir in lipophilic vesicular structure may be expected to enhance the ora... more Encapsulation of Ganciclovir in lipophilic vesicular structure may be expected to enhance the oral absorption and prolong the existence of the drug in the systemic circulation. So the purpose of the present study was to improve the oral bioavailability of Ganciclovir by preparing nanosized niosomal dispersion. Niosomes were prepared from Span40, Span60, and Cholesterol in the molar ratio of 1:1, 2:1, 3:1, and 3:2 using reverse evaporation method. The developed niosomal dispersions were characterized for entrapment efficiency, size, shape, in vitro drug release, release kinetic study, and in vivo performance. Optimized formulation (NG8; Span60:Cholesterol 3:2 molar ratio) has shown a significantly high encapsulation of Ganciclovir (89±2.13%) with vesicle size of 144±3.47 nm (polydispersity index [PDI]=0.08). The in vitro release study signifies sustained release profile of niosomal dispersions. Release profile of prepared formulations have shown that more than 85.2±0.015% drug was released in 24 h with zero-order release kinetics. The results obtained also revealed that the types of surfactant and Cholesterol content ratio altered the entrapment efficiency, size, and drug release rate from niosomes. In vivo study on rats reveals five-time increment in bioavailability of Ganciclovir after oral administration of optimized formulation (NG8) as compared with tablet. The effective drug concentration (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0.69 µg/mL in plasma) was also maintained for at least 8 h on administration of the niosomal formulation. In conclusion, niosomes can be proposed as a potential oral delivery system for the effective delivery of Ganciclovir.
Microemulsions are isotropic, thermodynamically stable transparent (or translucent) systems of oi... more Microemulsions are isotropic, thermodynamically stable transparent (or translucent) systems of oil, water, and surfactant, frequently in combination with a cosurfactant with a droplet size usually in the range of 20-200 nm. Since their discovery, they have attained increasing significance both in basic research and in industry. Due to their distinct advantages such as enhanced drug solubility, thermodynamic stability, facile preparation, and low cost, uses and applications of microemulsions have been numerous. Recently, there is a surge in the exploration of microemulsion for transdermal drug delivery for their ability to incorporate both hydrophilic (5-fluorouracil, apomorphine hydrochloride, diphenhydramine hydrochloride, tetracaine hydrochloride, and methotrexate) and lipophilic drugs (estradiol, finasteride, ketoprofen, meloxicam, felodipine, and triptolide) and enhance their permeation. Very low surface tension in conjunction with enormous increase in the interfacial area due to nanosized droplets of the microemulsion influences the drug permeation across the skin. A large number of oils and surfactants are available, which can be used as components of microemulsion systems for transdermal delivery but their toxicity, irritation potential, and unclear mechanism of action limit their use. Besides surfactants, oils can also act as penetration enhancers (oleic acid, linoleic acid, isopropyl myristate, isopropyl palmitate, etc.). The transdermal drug delivery potential of microemulsions is dependent not only on the applied constituents of the vehicle but also drastically on the composition/internal structure of the phases which may promote or hamper the drug distribution in the vehicles. This article explores microemulsion as transdermal drug delivery vehicles with emphasis on components selection for enhanced drug permeation and skin tolerability of these systems and further future directions.
The aim of the present study was to investigate the nanoemulsion system for enhanced percutaneous... more The aim of the present study was to investigate the nanoemulsion system for enhanced percutaneous penetration of domperidone. Pseudoternary phase diagrams were constructed in order to optimize the surfactant, cosurfactant and surfactant: cosurfactant weight ratios (Smix). Nine nanoemulsion formulations were selected, characterized and their ex-vivo permeation studies using rat skin were performed. The nanoemulsion formulations had small droplet size (<90 nm), uniform size distribution (PI, < 0.2) and low viscosity (<160 mP). The results demonstrated that the droplet size and viscosity of nanoemulsion decreased following decrease in the concentration of polysorbate 20, whereas transdermal flux was increased. The optimized formulation NE-B1, which contained oleic acid (4 % w/w), polysorbate 20 (10 % w/w), diethylene glycol monoethyl ether (20 % w/w) and water (64 % w/w) showed significant increase (P < 0.01) in the transdermal flux (169.32 ± 8.33 g.h -1 cm -2 ). The in vivo studies revealed a 3.5 fold increase in relative bioavailability through transdermal application of NE-B1 formulation compared to oral drug suspension. Moreover, the effective drug plasma concentration was maintained for 16 hour after the transdermal application indicated that the developed nanoemulsion systems could be a promising carrier for the transdermal delivery of domperidone for prolonged period.
Paracetamol is a sparingly soluble bitter tasting drug. It is widely used as an analgesic and ant... more Paracetamol is a sparingly soluble bitter tasting drug. It is widely used as an analgesic and antipyretic. Complexation of drug with different cyclodextrins (α, β and HP-β-CD) was attempted to improve solubility of Paracetamol. During the drug excipient interaction studies, α, β cyclodextrins elicited analytical interference and showed considerable absorbance at λmax (243.5 nm) of Paracetamol while the ones constituting of hydroxypropyl-beta-cyclodextrin (HP-β-CD) did not show any such interference. Therefore, the present study is concentrated on exploring HP-β-CD as complexing agent. Phase solubility studies showed that complexation of Paracetamol/HP-β-CD at molar ratio 1:1 and showed A L type solubility curve. Complexation was done by various methods like physical mixing, kneading and freeze drying and resulting drug complexes were characterized by Differential Scanning Calorimetry (DSC) and Fourier Transform Infrared Spectroscopy (FTIR). The thermograms obtained showed an endothermic peak for Paracetamol, for physical mixture to some extent for kneaded mixture, but was completely eliminated for freeze dried product (Inclusion complex). Similar results were obtained during IR studies. Therefore, solid inclusion complex of paracetamol prepared by freeze drying method was found to be an ideal complex. The solubility of paracetamol, was significantly increased (six folds of normal solubility) by complexation with HP-β-CD.
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