Rajendra Awasthi

Development of novel gastroretentive drug delivery system of gliclazide: hollow beads

Abstract Aim: The current communication deals with the development of hollow floating beads of gliclazide. The primary effect of this drug is to potentiate glucose-stimulated insulin release from pancreatic islet-β-cells by induction of a decrease in potassium efflux from these cells. Because of the poor aqueous solubility, its absorption is limited. Thus, an attempt was made to improve its release profile. Methods: The hollow drug-loaded alginate beads in combination with low methoxyl pectin and hydroxypropylmethylcellulose (HPMC) were prepared by a simple ionotropic gelation method. The beads were evaluated for particle size and morphology using optical microscopy and scanning electron microscopy (SEM), respectively. Mucoadhesion test was done using goat stomach mucosal membrane. Release characteristics of the gliclazide-loaded hollow beads were studied in 0.1 N HCl (pH 1.2) and phosphate buffer (pH 5.8). Results: The developed beads were spherical in shape with hollow internal structure and had a particle size in the range of 0.730 ± 0.05 to 0.890 ± 0.03 mm. The incorporation efficiency of alginate -pectin beads was higher than alginate -HPMC beads. The Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC) and X-ray diffraction analysis showed stable character of drug in the drug-loaded hollow beads and revealed the absence of any drug -polymer interactions. The beads remained buoyant for more than 12 h. The drug release from beads followed Fickian diffusion with swelling. Conclusion: The preliminary results of this study suggest that the developed beads containing gliclazide could enhance drug entrapment efficiency, reduce the initial burst release and modulate the drug release.

Development of novel gastroretentive floating particulate drug delivery system of gliclazide.

The objective of present project was to improve the dissolution profile of gliclazide by developing floating alginate beads using various biodegradable polymers like gelatin, pectin and hydroxypropylmethylcellulose (HPMC). The floating beads were prepared by a simple ionotropic gelatin method using calcium carbonate as gas generating agent. The developed beads were characterized by Fourier transform infrared spectroscopy analysis, differential scanning calorimetry, X-ray diffraction analysis and scanning electron microscopy (SEM). The prepared beads showed good in vitro floatation, which was dependent on the concentration of gas-forming agent. SEM photomicrographs confirmed that the developed beads were spherical in shape and had particle size in the range of 730 to 890 μm. The incorporation efficiency was found to be in the range of 59.96 to 85.1%. The cumulative percent drug release from the beads after 10 h dissolution study at pH 1.2 and pH 5.8 was in the range of 33 to 46% and 82 to 95% respectively. The concentration of the gas generating agent was found to influence the release rate. The mechanism of drug release was Fickian diffusion with swelling. The in vivo sub-acute hypoglycemic study in high fat diet induced diabetic C57BL/6J mice demonstrated significant (p < 0.05) hypoglycemic effect over a period of 12 h and 24 h, respectively, with HPMC and pectin beads. A significant (p & 0.05) reduction in fasting and non-fasting blood glucose levels, reduction in fasting plasma insulin level and a significant improvement in glucose tolerance were observed in animals treated with formulations. The developed beads were suitable carriers for improving the systemic absorption of gliclazide and maintaining reduced blood glucose levels.

Decades of research in drug targeting to the upper gastrointestinal tract using gastroretention technologies: where do we stand?

Abstract A major constraint in oral controlled release drug delivery is that not all the drug candidates are absorbed uniformly throughout the gastrointestinal tract (GIT). Drugs having “absorption window” are absorbed in a particular portion of GIT only or are absorbed to a different extent in various segments of the GIT. Thus, only the drug released in the region preceding and in close vicinity to the absorption window is available for absorption. The drug must be released from the dosage form in solution form; otherwise, it is generally not absorbed. Hence, much research has been dedicated to the development of gastroretentive drug delivery systems that may optimize the bioavailability and subsequent therapeutic efficacy of such drugs, as these systems have unique properties to bypass the gastric emptying process. These systems show excellent in vitro results but fail to give desirable in vivo performance. During the last 2–3 decades, researchers from the academia and industries are giving considerable importance in this field. Unfortunately, till date, few so-called gastroretentive dosage forms have been brought to the market in spite of numerous academic publications. The manuscript considers strategies that are commonly used in the development of gastroretentive drug delivery systems with a special attention on various parameters, which needs to be monitored during formulation development.

Potential therapeutic activity of Phlogacanthus thyrsiformis Hardow (Mabb) flower extract and its biofabricated silver nanoparticles against chemically induced urolithiasis in male Wistar rats

Urolithiasis is a painful disorder in which stones are formed in the kidney, bladder or urethra. There are no proper therapeutic treatments available for kidney stones and people suffering from larger stones have to undergo surgery which has many side effects. A natural remedy with therapeutic effects that can dissipate and remove even the larger stones would eliminate the need of a surgery and the risks associated with it. The flowers of Phlogacanthus thyrsiformis used in culinary recipes in the north eastern India are also widely used as a folklore medicine for the treatment of kidney stones and liver disorders. The aim of this study was to evaluate the prophylactic and therapeutic activity of the aqueous extract of P. thyrsiformis flowers and its biofabricated silver nanoparticles against struvite urinary stones and calcium oxalate kidney stones. A kidney stone inhibition study was carried out on struvite stones grown in gel medium and calcium oxalate stones in rat models using an aqueous extract of P. thyrsiformis flowers and its biofabricated silver nanoparticles. The aqueous extract of P. thyrsiformis flowers and their biofabricated silver nanoparticles, obtained by a green synthetic method, were used to treat struvite urinary stones in vitro and calcium oxalate kidney stones in vivo. Struvite stones were grown in tubes by gel diffusion technique and were treated with varying concentrations of the extract and its nanoparticles. The size of the struvite stones was monitored for 96h using a travelling microscope. Calcium oxalate stones were induced in male Wistar rats by feeding ethylene glycol-ammonium chloride mixture for 14days. Both, prophylactic and therapeutic activities were evaluated by analyzing the urine, serum and histopathological parameters of the rats. The qualitative screening of water extract unveiled the presence of flavonoids as a major constituent. Both, the extract and the nanoparticles effectively reduced the size of struvite stones in vitro and eliminated calcium oxalate stones in Wistar rats in vivo. The potent therapeutic activity of both extract and silver nanoparticles was observed as compared to preventive activity. Anti-urolithiatic potency can be attributed to the presence of flavonoids.

Hydrogel based Drug Delivery Systems: A Review with Special Emphasis on Challenges Associated with Decontamination of Hydrogels and Biomaterials

BACKGROUND Many researches involving the development of new techniques and biomaterials to formulate a suitable drug delivery system and tissue engineering have been conducted. The majority of published literature from these researches emphasizes the production and materials characterization. The safety aspect of hydrogels and biomaterials is a major constraint in their biological applications. OBJECTIVE The present review article aimed to summarize various literatures that encompass the difficulties encountered with decontamination and sterilization methods in the preparations of biomaterials and especially hydrogels for biological applications. METHOD We searched for original and review articles from various indexed journals reporting applications of hydrogels and biomaterials in drug delivery systems and the importance of decontamination process for hydrogel containing preparations based on various patents evidences. RESULTS Despite the vast literature available, limited information regarding the decontamination and sterilization processes related to hydrogels and biomaterials is reported. Sterilization processes to hydrogels are not yet fully explored. Researchers working on hydrogel based systems can consider decontamination of such biomaterial as an important tool to allow for commercialization within the chemical, herbal or pharmaceutical industries. CONCLUSION Unfortunately, till date, limited papers are available which reported the challenges associated with decontamination methods to prepare hydrogels and biomaterials for biological applications. In conclusion, each case of biomaterial requires individual consideration to decontamination and/or sterilization. This must be submitted to a specific method, but more than one technique can be involved. Physicochemical and biological alterations must be avoided and evaluated by the appropriate assays method. Furthermore, it is also important to consider that each method must be validated depending upon the process variables.

Dual crosslinked pectin–alginate network as sustained release hydrophilic matrix for repaglinide

Repaglinide, an oral antidiabetic agent, has a rapid onset of action and short half-life of approximately 1h. Developing a controlled and prolonged release delivery system is required to maintain its therapeutic plasma concentration and to eliminate its adverse effects particularly hypoglycemia. The present study aimed to develop controlled release repaglinide loaded beads using sodium alginate and pectin with dual cross-linking for effective control of drug release. The prepared beads were characterized for size, percentage drug entrapment efficiency, in vitro drug release and the morphological examination using scanning electron microscope. For the comparative study, the release profile of a marketed conventional tablet of repaglinide (Prandin® tablets 2mg, Novo Nordisk) was determined by the same procedure as followed for beads. The particle size of beads was in the range of 698±2.34-769±1.43μm. The drug entrapment efficiency varied between 55.24±4.61 to 82.29±3.42%. The FTIR results suggest that there was no interaction between repaglinide and excipients. The XRD and DSC results suggest partial molecular dispersion and amorphization of the drug throughout the system. These results suggest that repaglinide did not dissolve completely in the polymer composition and seems not to be involved in the cross-linking reaction. The percent drug release was decreased with higher polymer concentrations. In conclusion, the developed beads could enhance drug entrapment efficiency, prolong the drug release and enhance bioavailability for better control of diabetes.

Performance Survey and Comparison Between Rapid Sterility Testing Method and Pharmacopoeia Sterility Test

The sterility test described in pharmacopoeial compendia requires a 14-day incubation period to obtain a valid analytical result. Therefore, the use of alternative methods to evaluate the sterility of pharmaceuticals, such as the BacT/Alert® 3D system, is particularly interesting, because it allows a reduced incubation period and lower associated costs. Considering that the BacT/Alert® 3D system offers several culture media formulations developed for this microbial detection system, the present study was aimed to evaluate and compare the performance of BacT/Alert® 3D with the pharmacopoeial sterility test. There was no significant difference between the ability of the culture media to allow detection of microbial contamination. However, the rapid sterility testing method allowed a more rapid detection of the challenge microorganisms, which indicates that the system is a viable alternative for assessing the sterility of injectable products.

Development of Dehydration-Rehydration Liposomal System Using Film Hydration Technique Followed by Sonication

The purpose of this study was to prepare and characterize levocetirizine hydrochloride loaded liposome of by film hydration technique followed by sonication. Sorbitol was added to facilitate the hydration of dried liposome into vesicles or to prepare rehydration system. The liposomes were characterized for size, shape, entrapment efficiency, in vitro drug release and stability. The morphology of liposomes was characterized through a phase-contrast microscope and transmission electron microscope. The percent entrapment efficiency and particle size varied between 55.6 ± 0.21 to 81.2 ± 0.52 and 15.73 ± 0.99 to 24.52 ± 0.97 μm, respectively. The drug release increased at higher concentration of phospholipids. On the other hand, the drug release was decreased at higher concentration of cholesterol. The preliminary results of this study suggest that the developed multi-lamellar vesicles containing levocetirizine hydrochloride could enhance drug entrapment efficiency, reduce the initial burst release and modulate the drug release.

Nanoparticles in Cancer Treatment: Opportunities and Obstacles

In the United States, the estimated number of new cancer cases in 2018 will be approx. 1.7 million. Historically, combination chemotherapy has been the primary choice of treatment. However, chemotherapeutics have pharmaceutical limitations, among which include problems with stability and aqueous solubility. Likewise, dose limiting toxicity is significant with nonspecific toxicity to healthy cells, hair loss, loss of appetite, peripheral neuropathy and diarrhea being typical side effects. The emergence of Multidrug resistance (MDR) also presents s a significant challenge for the successful treatment of cancer whereby cancer cells become cross resistant to many of the chemotherapeutic agents used. Nanotechnology presents a new frontier for cancer treatment. It holds potential in minimizing systemic toxicity through the development of functionalized particles for targeted treatment. They also provide an alternative strategy to circumvent multidrug resistance as they have a capacity to by-pass the drug efflux mechanism associated with this phenotype. Aside from the advantages they offer in treatment, nanoparticles are also emerging to be valuable diagnostic entities. This article highlights the various ways nanotechnology is being used to improve the treatment and management of cancer. We also discuss the opportunities and obstacles in this area and provide an up to date review of progress in the treatment of cancer.

Antibacterial and in vitro Growth Inhibition Study of Struvite Urinary Stones Using Oxalis corniculata Linn. Leaf Extract and its Biofabricated Silver Nanoparticles

BACKGROUND Herbal drugs are gaining exponential scientific recognition due to their distinct advantages. In the last 2-3 decades, a gradual increase in worldwide patents on herbal nanoformulations has been noted to address the solubility and bioavailability issues of phytoceuticals. Struvite or ammonium magnesium phosphate hexahydrate (NH4MgPO4.6H2O) is among the important urinary infection stones causing painful urological ailment. These smaller stones may bind together to form bigger staghorn calculus. Urinary tract infections caused by some gram positive and gram negative bacteria further enhance the chance of formation of such stones. Oxalis corniculata Linn. is an edible plant, traditionally used in the treatment of bacterial infections and kidney stones. However, there is no scientific evidence to relate the use of O. corniculata against struvite kidney stones. Hence, the antibacterial and struvite stones inhibition activity of the aqueous extract of Oxalis corniculata Linn. leaves and its biofabricated silver nanoparticles (AgNPs) was studied. METHODS The aqueous extract of O. corniculata was prepared by Soxhlet extraction. AgNPs were synthesized using green technique and were characterized using UV and IR spectroscopy, XRD, TEM, DLS and zeta potential studies. Antibacterial activity of the aqueous extract and the silver nanoparticles was tested against E. coli (gram negative) and S. aureus (gram positive) species. Struvite stones were grown in a gel medium by in vitro single diffusion gel growth technique and its inhibition study was carried out using the extract and its biofabricated nanoparticles. RESULTS The aqueous extract and its biofabricated AgNPs exhibited potent antibacterial activity against both gram positive and gram negative strains of bacteria. The aqueous extract also effectively repressed the growth of struvite stones and led to the dissolution of stones, but the inhibitory effect was further enhanced by its biofabricated AgNPs. CONCLUSION The present work confirms the inhibitory activity of the aqueous extract of edible O. corniculata and its biofabricated silver nanoparticles against urinary tract infection (UTI) causing bacteria and urolithiasis. Therefore, the consumption of O. corniculata in our daily diet may reduce the risk of UTI and urolithiasis.