Hindu College of Pharmacy

The Drug Development and Therapeutics (DDT) is an open access peer-reviewed journal committed to publishing high-quality articles in the field of Drug synthesis and development and Therapeutics from industry, Clinicians and Academia.

Chapter in Book NATIONAL EDUCATION POLICY 2020: A REVIEW Edited by Dr. Shyam Khobraji Gore Dnyanopasak Shikshan Mandal’s Arts, Commerce, and Science College, Jintur. Dnyanopasak Shikshan Mandal’s Arts, Commerce, and Science College, Jintur PUBLICATION ISBN: 978-81-957387-2-4 Copyright © Dnyanopasak College Jintur First Published: 2023 Edition: I

The emerging trends in the combinatorial chemistry and drug design have led to the development of drug candidates with greater lipophilicity, high molecular weight and poor water solubility. Majority of the failures in new drug development have been attributed to poor water solubility of the drug. Issues associated with poor solubility can lead to low bioavailability resulting in suboptimal drug delivery. About 40% of drugs with market approval and nearly 90% of molecules in the discovery pipeline are poorly water-soluble. With the advent of various insoluble drug delivery technologies, the challenge to formulate poorly water soluble drugs could be achieved. Numerous drugs associated with poor solubility and low bioavailabilities have been formulated into successful drug products. Several marketed drugs were reformulated to improve efficacy, safety and patient compliance. In order to gain marketing exclusivity and patent protection for such products, revitalization of poorly soluble drugs using insoluble drug delivery technologies have been successfully adopted by many pharmaceutical companies. This review covers the recent advances in the field of insoluble drug delivery and business prospects.

Microencapsulation is one of the quality preservation techniques of sensitive substances and a method for production of materials with new valuable properties. Microencapsulation is a process of enclosing micron-sized particles in a polymeric shell. There are different techniques available for the encapsulation of drug entities. The encapsulation efficiency of the microparticle or microsphere or microcapsule depends upon different factors like concentration of the polymer, solubility of polymer in solvent, rate of solvent removal, solubility of organic solvent in water, etc. The present article provides a literature review of different microencapsulation techniques and different factors influencing the encapsulation efficiency of the microencapsulation technique.

The formulation of drugs is carried out with the principle objective of enhancing their bioavailability. Poorly water soluble drugs are challenging for the formulation scientists with regard to solubility and bioavailability. Lipid-based drug delivery systems (LBDDS) are one of the emerging technologies designed to address such challenges. Encapsulating or solubilizing the drug in lipid excipients can lead to increased solubilization and absorption, resulting in enhanced bioavailability. Recent advances in these formulation technologies have led to the successful commercialization of lipid-based formulations. This review provides a comprehensive summary and characterization of lipid-based formulations, especially for oral delivery, from both physicochemical and biopharmaceutical perspectives. This review also focuses on the processing techniques necessary to obtain solid lipid-based formulations for oral delivery, along with a brief discussion of lipid excipients and their characterization.

INTRODUCTION: Eudragit is the brand name for a diverse range of polymethacrylate-based copolymers. It includes anionic, cationic, and neutral copolymers based on methacrylic acid and methacrylic/acrylic esters or their derivatives. AREAS COVERED: In this review, the physicochemical characteristics and applications of different grades of Eudragit in colon-specific/enteric-coated/sustained release drug delivery and taste masking have been addressed. EXPERT OPINION: Eudragits are amorphous polymers having glass transition temperatures between 9 to > 150(o)C. Eudragits are non-biodegradable, nonabsorbable, and nontoxic. Anionic Eudragit L dissolves at pH > 6 and is used for enteric coating, while Eudragit S, soluble at pH > 7 is used for colon targeting. Studies in human volunteers have confirmed that pH drops from 7.0 at terminal ileum to 6.0 at ascending colon, and Eudragit S based systems sometimes fail to release the drug. To overcome the shortcoming, combination of Eudragit S and Eudragit L which ensures drug release at pH < 7 has been advocated. Eudragit RL and RS, having quaternary ammonium groups, are water insoluble, but swellable/permeable polymers which are suitable for the sustained release film coating applications. Cationic Eudragit E, insoluble at pH ≥ 5, can prevent drug release in saliva and finds application in taste masking.

Green chemistry has been an eye catching area of interest since the past few years. With the problem of energy crisis looming high and its constraint being particularly vulnerable on the developing economies, the need for giving alternative traditional chemistry a serious consideration as well as adequate room for development has received significant boost through the coveted efforts of multidisciplinary and interdisciplinary scientific fields. Nanoscience has been the right field in this dimension as it opens up the door to multiple opportunities through enabling a number of chemical, biochemical, and biophysical transformations in a significantly easier and reliable manner. The use of nanoparticles has made the fields of catalysis, synthesis, and enzyme immobilizations as well as molecular interactions a lot much easier, rapid and easily controllable. This review article sheds light on the popular alternative synthesis routes being employed for the synthesis of nanoparticles, the pivotal being from microbes, plants, and chemical routes via sonication, microwaving, and many others.

Desmodium gangeticum is herbal species which is widely used in the indigenous system of medicine and is reported to contain flavone and isoflavanoid glycosides. In view of its wide use and it's chemical composition, this study was aimed at examining the antioxidant activity of the extract of D. gangeticum. The extract was studied for diphenyl picryl hydrazyl (DPPH), nitric oxide, ferryl-bipyridyl and hypochlorous acid scavenging activity along with lipid peroxidation. Nitric oxide was generated using sodium nitroprusside and was studied using Griess reagent. In order to study the iron chelating capacity of the extract, the percentage ferryl-bipyridyl inhibition was studied. Hypochlorous acid scavenging activity was tested by measuring the inhibition of 5-thio-2-nitrobenzoic acid oxidation. The extract was also studied for lipid peroxidation assay by thiobarbituric acid-reactive substances (TBARS) method using rat brain homogenate. The results indicate that D. gangeticum extract has potent antioxidant activity.

The perturb and observe (P&O) algorithm is a simple and efficient technique, and is one of the most commonly employed maximum power point (MPP) tracking (MPPT) schemes for photovoltaic (PV) power-generation systems. However, under partially shaded conditions (PSCs), P&O method miserably fails to recognize global MPP (GMPP) and gets trapped in one of the local MPPs (LMPPs). This paper proposes ant-colony-based search in the initial stages of tracking followed by P&O method. In such a hybrid approach, the global search ability of ant-colony optimization (ACO) and local search capability of P&O method are integrated to yield faster and efficient convergence. A theoretical analysis of the static and dynamic convergence behavior of the proposed algorithm is presented together with computed and measured results.

Calendula officinalis Linn. (Asteraceae) is used medicinally in Europe, China and India amongst several places in the world. It is also known as “African marigold” and has been a subject of several chemicaland pharmacological studies. It is used in traditional medicine, especially for wound healing, jaundice, blood purification, and as an antispasmodic. Chemical studies have underlined the presence of variousclasses of compounds, the main being triterpenoids, flavonoids, coumarines, quinones, volatile oil, carotenoids and amino acids. The extract of this plant as well as pure compounds isolated from it, have been demonstrated to possess multiple pharmacological activities such as anti-HIV, cytotoxic, antiinflammatory, hepatoprotective, spasmolytic and spasmogenic, amongst others. In this review, we have explored the phytochemistry and pharmacological activities of C. officinalis in order to collate existinginformation on this plant as well as highlight its multi-activity properties as a medicinal agent. This is as a result of the worldwide cultivation of the plant and increasing published reports on it.

Drug delivery systems are becoming increasingly sophisticated as pharmaceutical scientists acquire a better understanding of the physicochemical and biochemical parameters pertinent to their performance. Over the past three decades, orally disintegrating tablets (ODTs) have gained considerable attention as a preferred alternative to conventional tablets and capsules due to better patient compliance. ODTs are solid dosage forms containing medicinal substances which disintegrate rapidly, usually in a matter of seconds, when placed on the tongue. Products of ODT technologies entered the market in the 1980s, have grown steadily in demand, and their product pipelines are rapidly expanding. New ODT technologies address many pharmaceutical and patient needs, ranging from enhanced life-cycle management to convenient dosing for paediatric, geriatric, and psychiatric patients with dysphagia. This has encouraged both academia and industry to generate new orally disintegrating formulations and technological approaches in this field. The aim of this article is to review the development of ODTs, challenges in formulation, new ODT technologies and evaluation methodologies, suitability of drug candidates, and future prospects.

Skin as an important site of drug application for both local and systemic effects. However in skin, the stratum corneum is the main barrier for drug penetration. Penetration enhancement technology is a challenging development that would increase the number of drugs availablefor transdermal administration. The permeation of drug through skin can be enhanced by both chemical penetration enhancement and physical methods. In this review, we have discussed the chemical penetration enhancement technology for transdermal drug delivery as well as the probable mechanisms of action.

India has a great wealth of various naturally occurring plant drugs which have great potential pharmacological activities. Datura stramonium (D. stramonium) is one of the widely well known folklore medicinal herbs. The troublesome weed, D. stramonium is a plant with both poisonous and medicinal properties and has been proven to have great pharmacological potential with a great utility and usage in folklore medicine. D. stromonium has been scientifically proven to contain alkaloids, tannins, carbohydrates and proteins. This plant has contributed various pharmacological actions in the scientific field of Indian systems of medicines like analgesic and antiasthmatic activities. The present paper presents an exclusive review work on the ethnomedical, phytochemical, pharmacological activities of this plant.

In the primitive era, humans benefited partially from plants and metals to treat microbial infections. Later these infections were cured with antibiotics but further suffered from resistance issues. In searching of an alternative, researchers developed an adjuvant therapy but were hampered by spreading resistance. Subsequently, nanoparticles (NPs) were proposed to cease the multi-drug resistant bacteria but were hindered due to toxicity issues. Recently, a novel adjuvant therapy employed metals and botanicals into innovative nanotechnology as nano-antibiotics. The combination of green synthesized metallic NPs with antibiotics seems to be a viable platform to combat against MDR bacteria by alleviating resistance and toxicity. This review focuses on the primitive to present era dealings with bacterial resistance mechanisms, newer innovations of nanotechnology and their multiple mechanisms to combat resistance. In addition, special focus is paid on greener NPs as antibiotic carriers, and their future prospects of controlled release and toxicity study.

Biosensing has been one of the hottest topic attracting scientific minds since long back. It is so as biological entities are very complex and are directly associated with the existence of a healthy environment. The design of biosensors also has witnessed significant changes in the recent past. Biosensors for applications as diverse as food quality estimation, environmental monitoring, and diagnosis of clinical and metabolic complications have come to the fore. Nanotechnology has bestowed some highly exciting ingredients for the improvement of sensing phenomenon. The use of diverse nanomaterials ranging from nanoparticles, nanotubes, nanorods, and nanowires has enabled faster detection and its reproducibility in a much better way. The unique properties of nanomaterials such as high electrical conductivity, better shock bearing ability, and the sensitive responses such as piezoelectric and versatile color based detection mechanisms are only the results of congregation of nanomaterial properties. This paper highlights the different types of biosensors based on different types of nanomaterials and their developmental and implicational aspects.

Diabetes mellitus occurrence has been associated to the modification of the physiological levels of glucose and is often accompanied by several long-term complications, namely neuropathy, nephropathy, retinopathy, cataract, and cardiovascular. Aldose reductase (AR) is an enzyme of aldoketo reductase super-family that catalyzes the conversion of glucose to sorbitol in the polyol pathway of glucose metabolism. In this context, aldose reductase inhibitors (ARIs) have received much attention worldwide. Decreased sorbitol flux through polyol pathway by ARIs could be an emerging target for the management of major complications of diabetes. The present review article describes a brief overview of the role of aldose reductase in the diabetic complications, advances achieved on ARIs and their potential use in the treatment and management of the major diabetic complications such as cataract, retinopathy, neuropathy, nephropathy and cardiovascular. The ARIs developed vary structurally, and representative structural classes of ARIs include i) carboxylic acid derivatives (such as Epalrestat, Alrestatin, Zopalrestat, Zenarestat, Ponalrestat, Lidorestat, and Tolrestat), ii) spirohydantoins and related cyclic amides (such as Sorbinil, Minalrestat, and Fidarestat), and iii) phenolic derivatives (related to Benzopyran-4-one and Chalcone). Among these inhibitors, Epalrestat is the only commercially available inhibitor till date. In addition, some other ARIs such as Sorbinil and Ranirestat had been advanced into late stage of clinical trials and found to be safe for human use. The role of various natural ARIs in management of diabetic complications will be discussed. Adapting ARIs could prevent sepsis complications, prevent angiogenesis, ameliorate mild or asymptomatic diabetic cardiovascular autonomic neuropathy and appear to be a promising strategy for the treatment of endotoxemia and other ROS-induced inflammatory diseases. The role of ARIs in non-diabetic diseases will also be discussed.

Behavioral tests are very useful to understand the Neuro-psychotic disease and also helpful in finding the treatment of the particular disease. Nowadays various tests are available to evaluate the anxiolytics effect of a new entity or even for comparative studies with the standard drug. As per the ethics, a new compound or drug believes to have possible pharmacological effects should be tested on animals before tested on humans which have similar physiology than humans. First, rats were used for behavioral test for evaluation of anti-anxiety drug but later on the various strain of mice were added for evaluation of anxiolytics because of better genetic possibilities than rats. In this review article, we have discussed the most commonly used behavioral tests used to evaluate the anti-anxiety effect. Anxiolytics are the agent which are used to elevate anxiety effect produced due to any cause. The various parameter will be undertaken for the better and precise evaluation of anxiolytics.

Plant derived biogenic synthesis of nanoparticles (NP) has been the recent trend in material science as featured sustainable catalysts. A great deal of the current nanocatalytic research has been oriented on the bio-inspired green catalysts based on their wide applicability. In this context, CuO NPs are synthesized following a green approach using an herbal tea (Stachys Lavandulifolia) flower extract. The phytochemicals contained in it were used asthe internal reductant without applying harsh chemicals or strong heat. The derived nanoparticles also got stabilized by the biomolecular capping. The as-synthesized CuO NPs was characterized over FT-IR, FE-SEM, EDS, TEM, XRD, TGA and UV-Vis spectroscopy. These NPs were exploited as a competent catalyst in the aryl and heteroaryl C-heteroatom (N, O, S) cross coupling reactions affording outstanding yields. The nanocatalyst was isolated and recycled in 8 consecutive runs with reproducible catalytic activity. Rigidity of the CuO/S. Lavandulifolia nanocomposite was further justified by leaching test and heterogeneity test.

Microemulsions are thermodynamically stable, transparent, colloidal drug carrier system extensively used by the scientists for effective drug delivery across the skin. It is a spontaneous isotropic mixture of lipophilic and hydrophilic substances stabilized by suitable surfactant and co-surfactant. The easy fabrication, long-term stability, enhanced solubilization, biocompatibility, skin-friendly appearance and affinity for both the hydrophilic and lipophilic drug substances make it superior for skin drug delivery over the other carrier systems. The topical administration of most of the active compounds is impaired by limited skin permeability due to the presence of skin barriers. In this sequence, the microemulsion represents a cost-effective and convenient drug carrier system which successfully delivers the drug to and across the skin. In the present review work, we compiled various attempts made in last 20 years, utilizing the microemulsion for dermal and transdermal delivery of various drugs. The review emphasizes the potency of microemulsion for topical and transdermal drug delivery and its effect on drug permeability.

PURPOSE: Niosomes play an increasingly important role in drug delivery as they can reduce toxicity and modify pharmacokinetic and bio-availability. Topically applied niosomes can increase the residence time of drugs in the stratum corneum and epidermis, while reducing the systemic absorption of the drug. It can act as drug containing reservoirs and the modification of the vesicular compositions or surface properties can adjust the drug release rate and the affinity for the target site. Ketoconazole is a broad spectrum Imidazole derivative useful in the treatment of superficial and systemic fungal infections. MATERIALS AND METHODS: In order to improve the low skin penetration and to minimize the side effects associated with topical conventional drug administration, Ketoconazole niosomes were prepared by a thin film hydration method using different ratios of non-ionic surfactants (Span 40, 60 and Tween 60) along with cholesterol (CHO). The formulations were evaluated for size, shape, entrapment efficiency and in vitro drug release. RESULTS: Niosomes appeared spherical in shape and size range was found to be 4.86 ± 1.24-7.38 ± 3.64 μm. The entrapment efficiency was found in the range of 55.14 ± 2.29-78.63 ± 0.91% and in vitro drug release in the range of 46.63 ± 0.95-72.37 ± 0.59% in 24 h. Ketoconazole niosomes formulated with Span 60 and CHO in the ratio of 1:0.2 were found to be promising and were incorporated into 1% Carbopol gel. The formulated gel was evaluated for various physicochemical parameters and antifungal activity. The in vitro drug release study was carried out using phosphate buffer saline pH 7.4 and was found to be 36.18 ± 1.50% in 12 h. CONCLUSION: Gel formulation containing niosomes loaded with Ketoconazole showed prolonged action than formulations containing Ketoconazole in non-niosomal form and it can be developed successfully to improve the antifungal activity.