Nano transfersomes vesicles of raloxifene HCl with sorbitan 80: formulation and characterization

Lipid vesicles in the nano range with ionic and nonionic surfactants are known as transfersomes. The presence of surfactant in the bilayer structure makes the vesicles very flexible in nature and helps them to permeate through the stratum corneum. The purpose of this research was to develop and characterize a transfersomal formulation of raloxifene HCl to deliver it into systemic circulation through the transdermal route. The transfersomal formulation was prepared by the rotary evaporation method with phospholipon 90G and sorbitan 80. The particle size, zeta potential and polydispersity index (PDI) of the formulation were measured. The drug entrapment efficiency (EE%) of the vesicles was determined by an indirect ultracentrifugation method. Differential scanning calorimetry (DSC), ex-vivo skin permeation study, field emission scanning electron microscope (FESEM), high resolution transmission electron microscope (HRTEM) and confocal laser scanning microscopy (CLSM) study were carried out as parts of advanced characterization of the developed formulation. The vesicles were found to have an average particle size of 95.1±1.05nm with a PDI value of 0.162±0.01 and zeta potential of +17.62±0.29 mV. EE% was recorded up to 90.9±1.15. Transdermal flux (J = 4.66±0.79 μg/cm2hr) of the developed formulation showed a favorable value required for the formulation efficacy. FESEM and TEM study results proved the spherical and round structures of the vesicles. DSC showed that the raloxifene was in the non-crystal form and was enclosed in the lipid bilayer. CLSM study proved the distribution of the drug in the stratum corneum, viable epidermis and dermis with high fluorescence intensity. The developed nano transfersomes of raloxifene HCl with sorbitan 80 showed encouraging results and can be further investigated for in vivo efficacy

Potential and future scope of nanoemulgel formulation for topical delivery of lipophilic drugs

The aim of this review is to evaluate and report the current potential and future scope of nanoemulgel formulation for becoming an effective delivery system for poorly water soluble drugs. In this review, we have summarized and discussed the outcome of different studies on permeability, pharmacokinetic, pharmacodynamic and safety profile of the drugs delivered topically through nanoemulgel. Rationality of use along with the major challenges to overcome for nanoemulgel formulation has been discussed. The Nanoemulgel drug delivery system is a formulation related intervention to improve the systemic delivery and therapeutic profile of lipophilic drugs. Nanoemulgel is an amalgamated formulation of two different systems in which nanoemulsion containing drug is incorporated into a gel base. The fusion of the two systems makes this formulation advantageous in several ways. Lipophilic drugs can be easily incorporated and the skin permeability of the incorporated drugs can be enhanced in several folds due to the finely distributed droplets of nanoemulsion phase. As a result, the pharmacokinetic and pharmacodynamic profiles of the lipophilic drugs are improved significantly. An increasing trend in nanoemulgel use in recent years has been noticed because of the better acceptability of the preparation to the patients due to their, noninvasive drug delivery, avoidance of gastrointestinal side effects, easier applicability and good therapeutic and safety profile. Despite of having few limitations, nanoemulgel formulation can be considered as a potential and promising candidates for topical delivery of lipophilic drugs in the future

A review on transdermal spray: formulation aspect

Transdermal spray offers numerous advantages over the other conventional transdermal drug delivery forms such as gel, ointment and patches, in terms of its cosmeceutical appearance, ready availability for application, flexibility in dosage design, less occurrence of skin irritation and faster drying rate from the application site due to the use of volatile solvent. However, compared to other transdermal drug delivery dosage forms, transdermal spray has the least and limited number of products approved for marketing. Among the drugs are, Evamist®, an estradiol formulation approved in 2007 by the FDA followed by Axiron® a non-spray solution to treat low testosterone in men and Recuvyra®, a pain reliever solution indicated for dogs. This review article focuses current status on the formulation and evaluation of transdermal spray in the background of the role and effects of its composition specially the selection of drugs, volatile solvents, penetration enhancers and film forming polymer, etc. The limitation of transdermal spray highlighted in this review is the concern of its use, especially, the third party exposure particularly for endocrinology indication. Moreover, transdermal spray is also restricted in drugs with large doses due to the limited diffusivity into the skin. The difficulty of exploiting hydrophilic drugs like peptides, macromolecules and new genetic treatments using DNA or small-interfering RNA (siRNA) into transdermal spray formulations is also a limitation that needs to be explored in depth

Stability-indicating RP-HPLC method for simultaneous quantitation of tramadol and aceclofenac in presence of their major degradation products: Method development and validation

Primary objective of this study was to develop a stability indicating reverse phase high performance liquid chromatography method for simultaneous quantitation of tramadol and aceclofenac in presence of their degradation products. The drugs were subjected to various International Conference on Harmonization recommended stress conditions, such as acid hydrolysis, alkaline hydrolysis, peroxide oxidation, thermolysis and photolysis. The major degradation products got well resoluted from the analytes in HPLC analysis with a mobile phase composed of a mixture of 0.01 M ammonium acetate buffer (pH 6.5) and acetonitrile (65:35, v/v) through a Phenomenex Gemini C18 (250 mm x 4.6 mm, 5 µm particle size) column. The method was linear over a range of 15-60 µg/ ml for tramadol and 40-160 µg/ ml for aceclofenac concentration. The analytes were detected at a wavelength of 270 nm. The method was validated and found to be specific, accurate, precise, stable and robust for its intended use. The method can be recommended for its future use in routine quality control, accelerated and real time stability analysis of the formulations containing tramadol and aceclofenac combination

Fast and simple gas chromatographic method for simultaneous estimation of camphor, menthol and methyl salicylate in analgesic ointment: application in stability study

A simple, rapid and sensitive gas chromatographic (GC) method with flame ionization detector (FID) has been developed and validated for simultaneous estimation of camphor, menthol and methyl salicylate (MS). Camphor, menthol and MS were separated at about 2.753, 3.206 and 3.995 min respectively on a capillary column with helium (3.3 ml/min) as carrier gas within 11 min run time. Noninterference of any peak with the peaks of interest confirms the selectivity of method. Derived quantitation limits (QL) were 0.847, 0.684 and 6.507 μg/ml for camphor, menthol and MS respectively. The linear relationship ( R2 > 0.999) between analyte concentration vs detector response was established within a range of QL to 150% of label claim concentration for each analyte. Recovery of each analyte at 50, 100 and 150% of label claim concentration levels were obtained within 99.67–101.53% establishing high accuracy of the method. The method showed acceptable precision with low relative standard deviation or RSD (0.24–1.03%) between percent recoveries for each analyte. RSD for intermediate precision (inter day analysis, analyst variation) was less than 1%. The validated method was successfully applied for quantitative determination of camphor, menthol and MS in stability samples of an analgesic ointment produced by IKOP Sdn. Bhd., Malaysia

Incorporation of carbopol to palm olein based analgesic cream: effect on formulation characteristics

The purpose of the investigation was to incorporate carbopol gel with palm olein based emulsion and to investigate the effect of such incorporation on formulation characteristics. A palm olein based emulsion was formulated followed by addition of carbopol 940 to it. The critical parameters of incorporating carbopol in bench scale level were checked. The developed palm olein-carbopol based analgesic cream was analyzed for pH, zeta potential, viscosity, rheological property and forced centrifugation.Incorporation of 0.3% of carbopol gel (1% w/w) helps to maintain the viscosity and stability. pH and zeta potential of palm olein-carbopol combined cream was within range of 6.90 to 7.20 and -23.1 to -74.9, respectively. Combination of palm olein based emulsion and carbopol would be a suitable option for topical cream formulation. The pH of carbopol gel and method of mixing with the palm olein based emulsion had crucial effects on phase separation of the product

Polymeric behavior evaluation of PVP K30- poloxamer binary carrier for solid dispersed nisoldipine by experimental design

Context: High melting point polymeric carrier without plasticizer is unacceptable for solid dispersion (SD) by melting method. Combined polymer–plasticizer carrier significantly affects drug solubility and tableting property of SD. Objective: To evaluate and optimize the combined effect of a binary carrier consisting PVP K30 and poloxamer 188, on nisoldipine solubility and tensile strength of amorphous SD compact (SDcompact) by experimental design. Materials and methods: SD of nisoldpine (SDnisol) was prepared by melt mixing with different PVP K30 and poloxamer amount. A 32 factorial design was employed using nisoldipine solubility and tensile strength of SDcompact as response variables. Statistical optimization by design expert software, and SDnisol characterization using ATR FTIR, DSC and microscopy were done. Results: PVP K30:poloxamer, at a ratio of 3.73:6.63, was selected as the optimized combination of binary polymeric carrier resulting nisoldipine solubility of 115 mg/mL and tensile strength of 1.19 N/m2 . Discussion: PVP K30 had significant positive effect on both responses. Increase in poloxamer concentration after a certain level decreased nisoldipine solubility and tensile strength of SDcompact. Conclusion: An optimized PVP K30–poloxamer binary composition for SD carrier was developed. Tensile strength of SDcompact can be considered as a response for experimental design to optimize SD

Pharmacokinetic and pharmacodynamic features of nanoemulsion following oral, intravenous, topical and nasal route

Abstract: Background: Most of the active pharmaceutical ingredients discovered recently in pharmaceutical field exhibits poor aqueous solubility that pose major problem in their oral administration. The oral administration of these drugs gets further complicated due to their short bioavailability, inconsistent absorption and inter/intra subject variability. Methods: Pharmaceutical emulsion holds a significant place as a primary choice of oral drug delivery system for lipophilic drugs used in pediatric and geriatric patients. Pharmacokinetic studies on nanoemulsion mediated drugs delivery approach indicates practical feasibility in regards to their clinical translation and commercialization. Results: This review article is to provide an updated understanding on pharmacokinetic and pharmacodynamic features of nanoemulsion delivered via oral, intravenous, topical and nasal route. Conclusion: The article is of huge interest to formulation scientists working on range of lipophilic drug molecules intended to be administered through oral, intravenous, topical and nasal routes for vivid medical benefits. Keywords: Hydrophobicity, oral delivery, pharmacokinetics, pharmacodynamics, routes of administration

Biocampatible supramolecular mesoporous silica nanoparticles as the next-generation drug delivery system

Supramolecular mesoporous silica nanoparticles (MSNs) offer distinct properties as opposed to micron-sized silica particles in terms of their crystal structure, morphology–porosity, toxicity, biological effects, and others. MSN biocompatibility has touched the pharmaceutical realm to exploit its robust synthesis pathway for delivery of various therapeutic molecules including macromolecules and small-molecule drugs. This article provides a brief review of MSN history followed by special emphasis on the influencing factors affecting morphology–porosity characteristics. Its applications as the next-generation drug delivery system (NGDDS) particularly in a controlled release dosage form via an oral drug delivery system are also presented and shall be highlighted as oral delivery is the most convenient route of drug administration with the economical cost of development through to scale-up for clinical trials and market launch

Carbamazepine gel formulation as a sustained release epilepsy medication for pediatric use

This study aimed to develop a carbamazepine (CBZ) sustained release formulation suitable for pediatric use with a lower risk of precipitation. The CBZ was first prepared as sustained release microparticles, and then the microparticles were embedded in alginate beads, and finally, the beads were suspended in a gel vehicle. The microparticles were prepared by a solvent evaporation method utilizing ethyl cellulose as a sustained release polymer and were evaluated for particle size, encapsulation efficiency, and release profile. The beads were fabricated by the dropwise addition of sodium alginate in calcium chloride solution and characterized for size, shape, and release properties. The gel was prepared using iota carrageenan as the gelling agent and evaluated for appearance, syneresis, drug content uniformity, rheology, release profile, and stability. The microparticles exhibited a particle size of 135.01 ± 0.61 µm with a monodisperse distribution and an encapsulation efficiency of 83.89 ± 3.98%. The beads were monodispersed with an average size of 1.4 ± 0.05 mm and a sphericity factor of less than 0.05. The gel was prepared using a 1:1 ratio (gel vehicle to beads) and exhibited no syneresis, good homogeneity, and good shearthinning properties. The release profile from the beads and from the gel was not significantly affected, maintaining similarity to the tablet form. The gel properties were maintained for one month real time stability, but the accelerated stability showed reduced viscosity and pH with time. In conclusion, CBZ in a gel sustained release dosage form combines the advantages of the suspension form in terms of dosing flexibility, and the advantages of the tablet form in regards to the sustained release profile. This dosage form should be further investigated in vivo in animal models before being considered in clinical trials