[show abstract][hide abstract] ABSTRACT: 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 flat thermogram of the nanoparticle data indicated that TQ formed a molecular dispersion within the nanoparticles. Optimized nanoparticles were evaluated further with the help of scintigraphy imaging, which ascertains the uptake of drug into the brain. Based on maximum concentration, time-to-maximum concentration, area-under-curve over 24 hours, and elimination rate constant, intranasal TQ-loaded nanoparticles (TQ-NP1) proved more effective in brain targeting compared to intravenous and intranasal TQ solution. The high drug-targeting potential and efficiency demonstrates the significant role of the mucoadhesive properties of TQ-NP1.
International Journal of Nanomedicine 01/2012; 7:5705-18. · 3.46 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
Drug Development and Industrial Pharmacy 11/2011; 38(1):84-92. · 1.54 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
Journal of Biomedical Nanotechnology 02/2011; 7(1):144-5. · 5.26 Impact Factor
[show abstract][hide abstract] ABSTRACT: Current investigation aimed to develop a novel Amiloride loaded mucoadhesive nanoemulsion formulation for nose-to-brain delivery. Furthermore, nasal irritation study and histopathological examination of the nasal mucosa were also carried out to assess nonirritant nature of the nanoemulsion. The optimized formulation, surface epithelium lining and the granular cellular structure of the nasal mucosa were totally intact, whereas KCl caused major changes in the ultrastructure of mucosa. Amiloride loaded mucoadhesive nanoemulsion formulations are non toxic on nasal mucosa and can be administered by intranasal route for effective treatment of epilepsy.
Journal of Biomedical Nanotechnology 02/2011; 7(1):142-3. · 5.26 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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 μg.h-1cm-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.
Current Nanoscience 10/2008; 4(4):381-390. · 1.36 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
Recent patents on drug delivery & formulation. 02/2008; 2(3):238-57.
[show abstract][hide abstract] ABSTRACT: 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. 02/2008; 2(3):275-89.
[show abstract][hide abstract] ABSTRACT: New drug discovery programs produce molecules with poor physico-chemical properties, making delivery of these molecules at the right proportion into the body a big challenge to the formulation scientist. The various options available to overcome the hurdle include solvent precipitation, micronisation/nanonization using high-pressure homogenization or jet milling, salt formation, use of microspheres, solid dispersions, cogrinding, complexation, and many others. Self-nanoemulsifying systems (SNES) form one of the most popular and commercially viable approaches for delivery of poorly soluble drugs exhibiting dissolution rate limited absorption, especially those belonging to the Biopharmaceutics Classification System II/IV. SNES are essentially an isotropic blend of oils, surfactants, and/or cosolvents that emulsify spontaneously to produce oil in water nanoemulsion when introduced into aqueous phase under gentle agitation. Conventional SNES consist of liquid forms filled in hard or soft gelatin capsules, which are least preferred due to leaching and leakage phenomenon, interaction with capsule shell components, handling difficulties, machinability, and stability problems. Solidification of these liquid systems to yield solid self-nanoemulsifying systems (SSNES) offer a possible solution to the mentioned complications, and that is why these systems have attracted wide attention. Other than the advantages and wide application of SSNEDS, the present paper focuses on formulation considerations, selection, and function of solidifying excipients; techniques of preparation; and case studies of drugs selected from different therapeutic categories. Developments in the techniques for in vitro evaluation of SSNEDS have also been discussed.
Critical Reviews in Therapeutic Drug Carrier Systems 02/2008; 25(1):63-116. · 2.68 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
Iranian Journal of Pharmaceutical Research. 01/2007;
[show abstract][hide abstract] ABSTRACT: The aim of present investigation was to develop novel oil-in-water (o/w) nanoemulsion based formulation containing atorvas-tatin for enhancing its oral bioavailability. Solubility of atorvastatin in oil, surfactant and co-surfactant was determined to select the for-mulation ingredients. Pseudo ternary phase diagrams were constructed by aqueous titration technique and various nanoemulsion formula-tions were prepared. Formulations taken from o/w nanoemulsion region were subjected to thermodynamic stability and dispersibility tests in order to eliminate metastable formulations in minimum possible time. In vitro drug release was performed by dialysis bag method and compared with the release of drug from suspension and conventional marketed tablet. The optimized formulation showed higher drug re-lease (99.34%), lower droplet size (42.8 ± 0.42 nm), lower polydispersity (0.237 ± 0.012), less viscosity (27.51 ± 1.01 cP) and infinite di-lution capability. A pharmacokinetic study was performed after oral administration of atorvastatin at 6 mg/kg in wistar rats. The area un-der the curve (AUC) and maximum plasma concentration (Cmax) in case of atorvastatin nanoemulsion were found 9-fold and 5-fold higher, respectively when compared to simple atorvastatin suspension. The present study illustrated the potential of nanoemulsion dosage form in improving biopharmaceutic performance of atorvastatin.