Sanju Nanda

Sonophoresis: recent advancements and future trends

Objectives Use of ultrasound in therapeutics and drug delivery has gained importance in recent years, evident by the increase in patents filed and new commercial devices launched. The present review discusses new advancements in sonophoretic drug delivery in the last two decades, and highlights important challenges still to be met to make this technology of more use in the alleviation of diseases.

Current Developments Using Emerging Transdermal Technologies In Physical Enhancement Methods.

Transdermal drug delivery using patches offers many advantages, but is limited primarily by the stratum corneum barrier. Amongst the various methods to overcome this barrier, physical methods are gaining in popularity and commercial devices development. Macroflux, MTS and Silex are based on microporation, involving use of microneedles that pierce thereby bypassing the stratum corneum. Intraject , Powderject and Helios are based on needleless jet injectors wherein very fine, solid particulate drug, is fired directly into the skin, using high-pressure gas. Med- Tats incorporate use of modified drug-containing tattoos, which bind to the skin, wherein the drug is absorbed. CHADD is based on use of heat, which increases skin - permeation of drugs. High-power, pulsed lasers transmit positive mechanical forces to the skin and create intercellular channels into the skin transiently. Sonophoresis involves use of ultrasound, which transiently disrupts the stratum corneum barrier. This technique offers a non-invasive transdermal extraction of interstitial fluids of sampling body fluids. Modified Liposomes include Ethosomes (containing alcohol) and Transferosomes (containing surfactants), which have enhanced skin permeability. Pulsed magnetic fields may create transient pores in cell membranes, including skin, resulting in increased permeation. Iontophoresis is based on application of electric potential for enhancing the movement of substances to and from the body. Dupel, Ionzyme, Liposite, ETrans, Phoresor and Drionic are based on iontophoresis. GlucoWatch offers non-invasive blood glucose monitoring, based on reverse iontophoresis. This review outlines recent commercial developments in physical transdermal drug delivery technology and the specific devices and applications being targeted by the pharmaceutical industry.

Broad-spectrum sun-protective action of Porphyra-334 derived from Porphyra vietnamensis

There are enormous UV-protective compounds present in the current world market, out of which 98% give protection against UV-B range and the remaining 2% are potent against far UV-A range only. Furthermore, these synthetic compounds have various problems related to photo-stability and cross-stability. There is a vital need of sunscreen agents that will remain stable for prolonged periods and provide broad-spectrum protection against harmful UV range. The Indian Ocean contains large amounts of macro-algae which synthesize varied amount of mycosporine amino acids, “sun-protective compounds” by shikmic acid pathway. In the present study, we have evaluated the sunscreen protection provided by Porphyra-334, a mycosporine amino acid isolated from Indian sp. of Porphyra. Furthermore, the isolated compound was detected by high performance thin layer chromatography (HPTLC) fingerprinting, high performance liquid chromatography (HPLC) and ultraviolet (UV), whereas nuclear magnetic resonance (NMR) spectroscopy and infrared spectrometry were used for its structural characterization. Stability studies were performed under different storage and pH conditions. Ultimately a sunscreen formulation was developed and its potential against marketed Aloe vera gel was evaluated by in vitro sunscreen protection method. It was observed that sunscreen potential of Porphyra-334 was 5.11-fold greater than that of the marketed Aloe vera gel preparation.

A validated high performance liquid chromatographic method for estimation of bromhexine and terbutaline in bulk and tablet dosage forms.

Introduction: Bromhexine (BH) is a mucolytic agent used in the treatment of respiratory disorders marketed in combination with terbutaline (TB), a β2-adrenergic receptor agonist used as a fast-acting bronchodilator. Materials and Methods: BH and TB were estimated at 270 nm by using ODS C8 column (length 250 mm and internal diameter 4.6 mm) as a stationary phase and a premix of phosphate buffer (0.05 M, pH 3): Acetonitrile (70:30 v/v) as a mobile phase. The total run time of this method was less than 20 min and the retention time for BH was found to be at 15.50 min while that of TB was 9.85 min at a flow rate of 1.0 ml/min, respectively. Results: Percentage label claim of tablet formulation using this method was found to be 99.35% for BH and 99.70% for TB, respectively. The standard deviation was found to be 0.225–0.351 for BH and 0.0.236–0.264 for TB for two different batches of tablet formulation. Conclusion: The results of analysis of two drugs from their tablet formulation using a developed method were found close to 100%. The low values of standard deviation indicate accuracy and reproducibility of the method. Thus developed methods can be used for the routine analysis of two drugs from a combined dosage form.

QbD-Based Development and Validation of a Stability-Indicating HPLC Method for Estimating Ketoprofen in Bulk Drug and Proniosomal Vesicular System

The current studies entail systematic quality by design (QbD)-based development of simple, precise, cost-effective and stability-indicating high-performance liquid chromatography method for estimation of ketoprofen. Analytical target profile was defined and critical analytical attributes (CAAs) were selected. Chromatographic separation was accomplished with an isocratic, reversed-phase chromatography using C-18 column, pH 6.8, phosphate buffer-methanol (50 : 50v/v) as a mobile phase at a flow rate of 1.0 mL/min and UV detection at 258 nm. Systematic optimization of chromatographic method was performed using central composite design by evaluating theoretical plates and peak tailing as the CAAs. The method was validated as per International Conference on Harmonization guidelines with parameters such as high sensitivity, specificity of the method with linearity ranging between 0.05 and 250 µg/mL, detection limit of 0.025 µg/mL and quantification limit of 0.05 µg/mL. Precision was demonstrated using relative standard deviation of 1.21%. Stress degradation studies performed using acid, base, peroxide, thermal and photolytic methods helped in identifying the degradation products in the proniosome delivery systems. The results successfully demonstrated the utility of QbD for optimizing the chromatographic conditions for developing highly sensitive liquid chromatographic method for ketoprofen.

Novel Carriers for Coenzyme Q10 Delivery

BACKGROUND Coenzyme Q10, a natural yellow benzoquinone, is a vitamin-like substance commonly found in blood and inner mitochondrial and cellular membranes. It is a natural antioxidant principle which plays an essential role in maintaining several biochemical pathways of body. It has exhibited many pharmacological activities in chronic heart failure, cardiofaciocutaneous syndrome, diabetes mellitus, carcinomas, autoimmune disease, cataract, asthma, periodontal disease and thyroid disorders. Moreover, it has demonstrated efficacy as nutritional supplement, in addition to its relevance in cosmetics. OBJECTIVE Coenzyme Q10 is a potent molecule but its high molecular weight and low aqueous solubility hamper its use as a therapeutic agent. Therefore, various novel drug delivery systems have been explored and developed to overcome these limitations in literature. Hence, objective of this review is to summarize the recent works on design and development of novel drug delivery systems for CoQ10, which include liposomes, polymeric nanoparticles, polymeric micelles, solid lipid nanoparticles, nanostructured lipid carriers, self-emulsifying drug delivery systems, nanoemulsions, solid and aqueous dispersions. Further, an account of pharmaceutical studies has also been given. RESULTS & CONCLUSION The reported studies indicate the promise of nanotechnology in enhancing the therapeutic value of CoQ10, promoting its usage as first line therapeutic agent, thus, revolutionizing its role in current medical therapy. The application of CoQ10 in pharmaceutical industry has grown tremendously in the past decade, due to its versatile nature. The successful application of this molecule in medicine, cosmetics and nutraceuticals points the way for its future development.

A validated sensitive liquid chromatographic method for the estimation of Sumatriptan succinate in bulk drug and tablet dosage form

Aim: The present study was undertaken to develop a validated, sensitive, rapid, simple and economic an isocratic HPLC method for estimating Sumatriptan succinate in tablet dosage form. Materials and Methods: Normal phase chromatographic analysis was performed on an Ascentis® Si HPLC Column (25cmΧ2.1mm, 5μm) with ammonium phosphate − acetonitrile (80:20, v/v, pH 3.5 adjusted with ortho-phosphoric acid) at a flow rate of 1 ml/min and detection wavelength of 230 nm. System suitability tests essential for the assurance of quality performance of the method were performed. The method was validated for accuracy, precision, reproducibility, specificity, and robustness, limit of detection (LOD), and limit of quantification (LOQ), as per International Conference on Harmonization (ICH) guidelines. Results: A single sharp peak was obtained for Sumatriptan succinate at retention time of 6.8±0.01 min. The polynomial regression data for the calibration plots exhibited good linear relationship (r=0.9999) over a concentration range of 50-1050 ng/ml and the linear regression equation was y=120.9x+33.56. Accuracy ranged from 99.96% to 101.49%. The LOD and LOQ values were 11 and 35 ng/ml, respectively. Conclusion: The proposed method gave good resolution of Sumatriptan succinate. System suitability tests and statistical analysis performed prove that the method is precise, accurate and reproducible, and hence can be employed for routine analysis of Sumatriptan succinate in bulk and commercial formulations.

Systematically optimized coenzyme q10-loaded novel proniosomal formulation for treatment of photo-induced aging in mice: characterization, biocompatibility studies, biochemical estimations and anti-aging evaluation

Abstract Environmental stress and advancing age is considered as the main cause of skin aging. However, environmental stress (especially UV radiations) accelerates the process of skin aging by manifolds. Coenzyme Q10 (CoQ10), an essential compound of cellular bioenergetics also acts as a strong antioxidant and protects the body against aging. High molecular weight and structure specific lipophilic nature of this molecule is a bottle neck in effective delivery through topical route. Preparation of a novel proniosomal (PN) gel formulation of CoQ10 employing systematic design of experiment (DoE) approach is a step ahead in transcending the constraints of the topical delivery. I-optimal mixture design was employed for systematic optimization of proniosomal formulation and evaluation of experimental data was performed for entrapment efficiency and in vitro release. Hydration of PN gel formulation with phosphate buffer (pH 7.5) results in submicron niosomes vesicles of spherical shape, which appeared dark against bright surroundings in TEM study. Animal skin was treated with UV radiations followed by treatment of PN gel CoQ10 and conventional CoQ10 present in a gel base. The effectiveness of the treatment was evaluated on the basis of biochemical estimation and histopathological studies. By using CoQ10 PN gel formulation, levels of superoxide dismutase (SOD), catalase (CA), glutathione (GSH) and total proteins were restored by 81.3%, 72.1%, 74.8 and 77.1%, respectively to that of control group. Histopathological studies revealed better protection of skin treated with CoQ10 PN gel compared to free CoQ10. Prepared PN gel was found undisturbing with the normal histology hence, tolerated by animal skin compare to conventional gel.

Transdermal Innovations in Diabetes Management

Diabetes mellitus, an endocrine disorder affecting glucose metabolism, has been crippling mankind for the past two centuries. Despite the advancements in the understanding pertaining to its pathogenesis and treatment, the currently available therapeutic options are far from satisfactory. The growing diabetic population increases the gravity of the situation. The shortcomings of the conventional drug delivery systems necessitate the need to delve into other routes. On account of its merits over other routes, the transdermal approach has drawn the interest of the researchers around the world. The transdermal drug delivery systems are aimed to achieve therapeutic concentrations of the drug through skin. These systems are designed so that the drug can be delivered at a pre-determined and controlled rate. This makes it particularly conducive to treat chronic disorders like diabetes. Correspondingly, the adverse effects and inconvenience concomitant with oral and parentral route are circumvented. This article attempts to outline the development of transdermal drug delivery systems to optimize diabetes pharmacotherapy. It not only covers the transdermal approaches adopted to fine-tune insulin delivery, but also, discusses various transdermal drug delivery systems fabricated to improve the therapeutic performance of oral hypoglycaemic agents. Such formulations include the advanced drug delivery systems, namely, transferosomal gels, microemulsions, self-dissolving micropiles, nanoparticles, insulin pumps, biphasic lipid systems, calcium carbonate nanoparticles, lecithin nanoparticles; physical techniques such as iontophoresis and microneedles and, drugs formulated as transdermal patches. In addition to this, the authors have also shed light on the future prospects and patented and commercial formulations of antidiabetic agents.

Spectrophotometric estimation of solifenacin succinate in tablet formulations.

Aim: The aim of this study is to develop a simple, sensitive, rapid, accurate, and precise spectrophotometric method for the estimation of solifenacin succinate in tablet dosage forms. Materials and Methods: For methods I and II, in a series of 10 ml volumetric flasks, aliquots of standard drug solution (100 μg/ml) in double distilled water were transferred and diluted with the same so as to give several dilutions in the concentration ranges of 10 – 60 μg/ml and 10 – 60 μg/ml, respectively, of solifenacin succinate. To 5 ml of each dilution taken in a separating funnel, (5 ml of bromo thymol blue for method I and 5 ml of bromo phenol blue for method II) reagent and 5 ml of chloroform were added. The reaction mixture was shaken gently for five minutes and allowed to stand so as to separate the aqueous and chloroform layers. The absorbance maxima were measured at 415.6 nm and 412 nm for methods I and II, respectively. Results: The recovery studies were found close to 100%, which indicates the accuracy and precision of the proposed methods. Statistical analysis was carried out, the results of which were found to be satisfactory. Standard deviation values were found to be low and that indicated the reproducibility of the proposed methods. Conclusion: The results indicated that both methods could be used for the routine estimation of solifenacin succinate from tablet formulations.