DEVELOPMENT AND VALIDATION OF A SIMPLE HPLC METHOD FOR ESTIMATION OF MYCOPHENOLATE MOFETIL IN MICROEMULSION FORMULATION

Objective: The present study deals with the development, validation and application of a simple, precise and accurate HPLC method for the determination of mycophenolate mofetil in pharmaceutical formulations and microemulsions. Methods: In this method, a simple isocratic mobile phase composition of methanol and water (75:25 v/v) pumped at 1 ml/minute flow rate through Phenomenex C18 column (dimension: 250 4.6 mm and 5 µm particle size) was used. Injection volume was 20 µl and analysis of mycophenolate mofetil was carried out at 250 nm. Results: The coefficient of regression was found to be 0.9996, indicating the linearity of the developed method within a range of 0.1 to 10 µg/ml. The limit of detection (LOD) and the limit of quantization (LOQ) were found to be 3.660ng/ml and 11.091ng/ml, respectively. The results showed that % deviation for change in compositions of the mobile phase, flow rate and temperature was within a range of-5.51 to 10.99%,-3.70 to 8.80% and-5.29 to 10.90%, respectively. The method seemed sensitive to change of temperature (±5 ○C) and methanol composition (±2%) as the results were at the boundary limit of 10% deviation. Conclusion: A simple, precise and accurate HPLC method for the determination of drug content from microemulsion has been developed and validated in accordance with ICH guidelines

Pharmaceutical application of solid dispersion technology in improving solubility of poorly soluble drugd : a review

Together with the permeability, the solubility of a drug plays an important role in determining its oral bioavailability. Nowadays, a majority of the new chemical entities are poorly water soluble candidates. For formulation scientists, it is a big deal to handle those drug candidates in order to formulate a stable pharmaceutical dosage form with appropriate bioavailability. To increase the oral bioavailability of poorly soluble drugs, so far formulation scientists have adopted many chemical and formulation approaches. Out of those approaches, solid dispersion has played an important role for the past few decades. There are many formulation strategies employed to prepare solid dispersions. Solid dispersion mainly increases solubility and dissolution characteristics and thereby also oral bioavailability of poorly soluble drugs. The present review article deals with different strategies of solid dispersion preparation techniques, problems associated with those techniques and how to overcome them in order to improve the solubility as well as bioavailability ofpoorly water soluble drugs

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

Formulation and optimization of raloxifene loaded nanotransfersomes by response surface methodology for transdermal drug delivery

Raloxifene HCl loaded transfersomes were fabricated, optimized, and characterized as carrier for transdermal delivery to overcome the poor bioavailabilty issue with the drug. Response surface methodology (RSM) was applied for optimization of the formulation with Box-Behnken experimental design. Phospholipid PC90G (A), sodium deoxycholate (SDC) (B) and sonication time (C), each at three levels, were selected as independent variables while entrapment efficiency (EE%) (Y1), vesicle size (Y2), and transdermal flux (Y3) were the response variables. The optimized formulation was further characterized for vesicular size distribution, shape, surface morphology, and zeta-potential. Response variables data were analyzed by Design expert® software and the best model for all three response variables was found to be quadratic. Formulation No13 with composition of 300mg PC90G (A), 35mg SDC (B) and 15min sonication time (C) was predicted as the optimized formulation. The optimized formulation resulted a particle size of 134±9.0 nm with 91±4.9% EE%, 6.5±1.1μg/cm2/h transdermal flux, and -2.61±0.5 mV zeta potential. Transmission electron microscopy, scanning electron microscopy, and dynamic light scattering study defined transfersomes as spherical,unilamellar structures with a homogenous distribution and low polydispersity index (0.080±0.021). Transfersomal formulation proved significantly superior in terms of amount of drug permeated and deposited in the skin, with an enhancement ratio of 6.25±1.5 and 9.25±2.4 when compared with conventional liposomes and ethanolic phosphate buffer solution of the drug respectively. Confocal scanning laser microscopy proved an enhanced permeation of coumarin-6 loaded transfersomes to the deeper layers of the skin (160 μm) as compared to the rigid liposomes (60 μm). These in-vitro findings proved that raloxifene HCl loaded transfersomal formulation could be a superior alternative to oral delivery of the drug

A REVIEW ON CO-PROCESSED EXCIPIENTS: CURRENT AND FUTURE TREND OF EXCIPIENT TECHNOLOGY

There is no single-component excipient fulfills all the requisite performance to allow an active pharmaceutical ingredient to be formulated into a specific dosage form. Co-processed excipient has received much more attention in the formulation development of various dosage forms, specially for tablet preparation by direct compression method. The objective of this review is to discuss the emergence of co-processed excipients as a current and future trend of excipient technology in pharmaceutical manufacturing. Co-processing is a novel concept of combining two or more excipients that possess specific advantages that cannot be achieved using a physical admixture of the same combination of excipients. This review article discusses the advantages of co-processing, the need of co-processed excipient, general steps in developing co-processed excipient, limitation of co-processed excipient, technologies used in developing co-processing excipients, co-processed excipients in the literature, marketed products and future trends. With advantages offered by the upcoming newer combination of excipients and newer methods of co-processing, co-processed excipients are for sure going to gain attraction both from academia and pharmaceutical industry. Furthermore, it opens the opportunity for development and use of single multifunctional excipient rather than multiple excipients in the formulation

Experimental design and optimization of raloxifene hydrochloride loaded nanotransfersomes for transdermal application

Raloxifene hydrochloride, a highly effective drug for the treatment of invasive breast cancer and osteoporosis in post-menopausal women, shows poor oral bioavailability of 2%. The aim of this study was to develop, statistically optimize, and characterize raloxifene hydrochloride-loaded transfersomes for transdermal delivery, in order to overcome the poor bioavailability issue with the drug. A response surface methodology experimental design was applied for the optimization of transfersomes, using Box-Behnken experimental design. Phospholipon ® 90G, sodium deoxycholate, and sonication time, each at three levels, were selected as independent variables, while entrapment efficiency, vesicle size, and transdermal flux were identified as dependent variables. The formulation was characterized by surface morphology and shape, particle size, and zeta potential. Ex vivo transdermal flux was determined using a Hanson diffusion cell assembly, with rat skin as a barrier medium. Transfersomes from the optimized formulation were found to have spherical, unilamellar structures, with a homogeneous distribution and low polydispersity index (0.08). They had a particle size of 13

Transdermal permeation mechanism of sodium deoxycholate aided nano-transfersomes by Differentail Sacnning Calorimetry (DSC)

Transfersomes are lipid based nano-vesicles made of phospholipid and surfactant. Their drug permeation mechanism through the skin has been attributed to the moisture seeking tendency (xerophobia) of the lipid vesicles followed by destabilization of lipid bi-layer in the stratum corneum (SC) by surfactant1. However, structural changes of SC due to surfactant need further elucidation to know the specific role of that surfactant in doing so. The objective of this study was to evaluate drug permeation mechanism of raloxifene loaded nano-transfersomes containing sodium deoxycholate used as a surfactant. Phospholipon® 90G was used as a lipid composition in the nano-formulation2. Three different types of skin i.e. mice, guineapig, and rabbit were used for this study. The SC was detached from the rest of the skin layers with chemical treatment, thoroughly washed, and kept for drying in a vacuum desiccator. The SC samples were subjected to an ex-vivo permeation study of the transfersomal formulation for 8 hours. A control sample was prepared in a similar way, without any formulation treatment. A sample of the SC section was cut, sealed in aluminum hermetic pans and scanned using DSC at a scanning rate of 5°C per minute over the range of 25°C–125°C. The characteristic bi-layer lipid and keratin transition peaks found in the control SC samples were: 75°C, 78°C, and 95°C for mice; 820C, 900C, and 990C for guineapig; and 840C, 920C, 990C for rabbit3. However, upon treatment with sodium deoxycholate aided raloxifene nano-transfersomes, most of the peaks were shifted towards lower melting points and some of them were disappeared. This finding confirmed disruption of lipid bi-layer and denaturation of keratin in the SC layer of the investigated skin samples by nano-transfersomes with sodium deoxycholate. It also established the role of sodium deoxycholate in transdermal permeation of drug loaded nano-transfersomes formulation

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