Dr. Farzaneh Mohamadpour
Department of Organic Chemistry, University of Sistan and Baluchestan, Iran.

ISBN 978-93-5547-666-1 (Print)
ISBN 978-93-5547-667-8 (eBook)
DOI: 10.9734/bpi/capr/v6

This book covers key areas of Pharmaceutical Research.  The contributions by the authors include Bosentan hydrochloride, self microemulsifying drug delivery system, pharmacokinetics parameters, spray drying, ultrasonic interferometer technology, Diabetes mellitus, silver nanoparticles, glycogenesis, metabolism, Solid lipid nanoparticle, nanocarriers,  nanotechnology, Alzheimer’s disease, drug design, computational modeling, artificial intelligence , artificial neural networks , Molecular hybridization, indolyl chalcone, micro tubulin inhibitors, antimitotic agent,  apoptosis, anti-inflammatory, intrinsic pathway, extrinsic pathway, Donepezil, methylphenidate, haloperidol, stereotypy,  immunohistochemistry,  neurological deficits, COVID-19, antimicrobial resistance,  azithromycin, chloroquine, antibiotic stewardship, Trace elements, phytoconstituents, stem barks, and Micronutrients. This book contains various materials suitable for students, researchers and academicians in the field of Pharmaceutical Research.

Media Promotion:


Bosentan Hydrochloride (BOS) is poorly water soluble, high molecular weight and eleven hydrogen bond acceptors. Thus, it exhibits poor bioavailability. A new Solid-Self Emulsifying Drug Delivery System (S-SMEDDS) of BOS has been successfully developed to enhance its oral bioavailability by improving its solubility and facilitating high molecular weight of BOS absorption. The primary composition of SMEDDS formulation was selected from solubility, pseudoternary phase diagram, emulsifying efficiency and compatibility test confirmed the suitability of Capmul MCM as oil, Tween 20 as surfactant and Propylene glycol as a co-surfactant for preparation of Liquid-Self Emulsifying Drug Delivery System (L-SMEDDS). The formulation of the BOS loaded L-SMEDDS were prepared in different concentration of oil, surfactant/co-surfactant and optimized by various evolutionary parameter such as robustness to dilution, drug content, ultrasonic interferometer, ease of emulsification, droplet size and in vitro diffusion study. The optimized L-SMEDDS converted into free flowing granules by spray drying technique. S-SMEDDS powder undergoes for characterization and confirmed the no interaction between drug and excipients. The S-SMEDDS powder compressed with variable concentration of directly compressible excipients. S-SMEDDS formulations were employing for both pre-compression and post-compression parameters. In vitro drug release study indicated that significant increased dissolution rate of the drug by all S-SMEDDS tablets versus the marketed formulation. In vivo studies in Sprague-Dowley rat for the optimized formulation was performed and compared to Marketed formulation observe significant increase the Cmax and AUC of BOS compared to Marketed formulation (P>0.05). Thus, the present investigation improved the oral bioavailability of BOS.

Antidiabetic Effects of Metal Nanoparticles in Rodents

Marjan Assefi, Nadeem Kizilbash, Naila Mahmood, Sohila Nankali, A. Nankali, Gholamreza Abdi

Challenges and Advances in Pharmaceutical Research Vol. 6, 29 August 2022, Page 37-45

Many people suffer from Diabetes Mellitus all over the world. It is a metabolic disorder that results in high blood Glucose level and is a multi-factorial problem marked by hyperglycemia due to decreased Insulin production or increased Insulin resistance. The restorative effect of Zinc Oxide and Silver nanoparticles on Streptozotocin-induced diabetic rodents has been investigated by numerous studies. The metal nanoparticles play an important role in clinical and natural applications. Although, Silver is an important metal used by many metabolic processes, very little information is available about the effect of Silver or Silver nanoparticles (SNPs) on Glucose metabolism. The reported results by various studies reveal a decrease in blood Glucose level of diabetic rodents treated with ZnONPs, Silver nanoparticles (SNPs) and Insulin.

Solid Lipid Nanoparticles: Preparation, Characterization and Applications- A Look Back

M. Swamivelmanickam, S. Sivakrishnan, R. Suresh

Challenges and Advances in Pharmaceutical Research Vol. 6, 29 August 2022, Page 46-60

Solid Lipid Nanoparticle [SLN] are numerous potential applications in the rapidly developing field of nanotechnology, including drug delivery, research and clinical medicine, and other diverse science and technology fields. Active pharmaceutical ingredients under development are often poorly water soluble and poorly bioavailable. SLN may be used to produce novel therapies because of their unique size-dependent characteristics. Traditional medication delivery technologies have certain limitations, and nanotechnology aims to eliminate such limitations. The therapeutic potential of solid lipid nanoparticles is intriguing. Preparation with lipids that can be tolerated by the body is their primary advantage. Nano-carriers that range in size from 10 to 1000 nanometres are known as Solid Lipid Nanoparticles. In an effort to overcome the shortcomings of polymeric nanoparticles, SLNs were introduced. A new formulation method was discovered by substituting lipids for polymers made from lipid nanoparticles. SLN in drug delivery examined in terms of potential advantages and disadvantages, as well as preparation methods and the principle behind drug release. SLNs in drug delivery are also characterised and applied. Nanometre-sized lipid particles are dispersed in water or surfactant solution in the form of "solid" or "liquid" lipids (SLNs). Hydrophilic and lipophilic drugs can now be delivered using SLN technology. The bioavailability of medications may also be improved with the use of SLNs. Adding drugs to nanocarriers provides a new method for delivering drugs to multiple levels of a patient's body. As a result, solid lipid nanoparticles have piqued researchers' interest due to their potential for delivering drugs in a regulated and targeted manner.

The study aims to modify current medications of Alzheimer’s disease (AD) with the use of our computational modeling methods. The modifications are designed to enhance the binding affinity of the newly designed drugs to protein molecules involved in Alzheimer’s, measured by the half maximal inhibitory concentration (IC50) value. This value is a measure of the concentration needed for the drug to inhibit a specific biological function. Two techniques are used to predict the anticipated modified IC50 values. First, by using the energies and the experimentally determined IC50 values, the functional graph approaches create correlations that lead to projected IC50 values for the changed drug molecules. The second approach in this research predicted the IC50 values of changed drug compounds using an artificial intelligence programme called NETS. Four modified drug molecules produced promising results in which the IC50 values were enhanced by one order of magnitude or more. The findings demonstrate that computational modelling can be a novel, time-saving, and great step in drug discovery.

Molecular hybridization is one of the frequently used rational drug design strategies to produce novel ligands. The newly created pharmacophores' biological activity is amplified by the molecular hybridization strategy, and the negative effects caused by the separate components is diminished. At three tubulin colchicine receptors, which are reportedly the targets for anticancer therapy, thirty variants of N-1 substituted indolyl chalcone of N-1 substituted 2-Acetyl Benzimidazole were provisionally docked. When combined, a novel scaffold was shown and it has the potential to be a strong tubulin inhibitor. Discovery and development of novel tubulin polymerization inhibitors is an urgent need in clinical research.

The study evaluated the effect of MLIF on extrinsic and intrinsic apoptosis pathways human CD4+ T lymphocytes. Cells were grown for 24 hours in either plain RPMI-1640 medium (control) or RPMI medium adding actinomycin D, MLIF, PMA, or any combination of the four. Cells treated with MLIF or PMA + MLIF did not substantially differ from control cells in medium during early apoptosis, according to annexin V/propidium iodide-stained cells; in contrast, cells treated with PMA or PMA + MLIF revealed significant differences from the control during delayed apoptosis. However, compared to the control, cells treated with PMA and PMA + MLIF exhibited a significant increase in cytochrome c and caspase 3 levels, indicating that this poor induction of cell death is controlled by the intrinsic pathway of apoptosis. Cytochrome c and caspase 3 levels in cells treated with MLIF showed no significant differences from control cells. Any of the therapies used did not result in the detection of the Fas receptor in cell culture, indicating that the extrinsic mechanism of apoptosis is not engaged. Human CD4+ T cells do not undergo apoptosis when exposed to MLIF; nevertheless, PMA and MLIF may also have an impact on the modest amounts of cell death seen during the late apoptosis phase. Because of its tiny size, MLIF functions as a natural, biological anti-inflammatory substance produced in axenic cultures of Entamoeba histolytica, which makes it a promising candidate for potential clinical applications.

Determining the Effects of Donepezil in Psychotic Disorders Using Swiss Albino Mice

Hemant Tanwani, Ritesh Churihar, Sameer Pandit

Challenges and Advances in Pharmaceutical Research Vol. 6, 29 August 2022, Page 103-113

Several antipsychotic medications are being used to treat schizophrenia as a psychotic illness. Donepezil, a medication for Alzheimer's disease that enhances cognition, is now approved. We therefore attempted to evaluate its significance for the mouse methylphenidate-induced psychosis models.
To induce psychosis in Swiss albino mice (n=6), 5 mg/kg methylphenidate was administered intraperitoneally (i.p). Donepezil was given at a dose of 1 mg/kg alone and in combination with 0.1 mg/kg haloperidol, and groups were compared with haloperidol 0.2 mg/kg. Donepezil's activity was also evaluated using the haloperidol-induced catalepsy test. ANOVA was used for statistical analysis, followed by the Bonferroni's test.
Methylphenidate, like amphetamine, successfully induced stereotypic behaviour in mice. Donepezil 1 mg/kg and haloperidol 0.2 mg/kg both significantly reduced stereotypy behaviour, with no statistically significant difference (p<0.05). Donepezil's effects were only marginally inferior to standard, while its combination (1 mg/kg with haloperidol 0.1 mg/kg) produced comparable results to standard haloperidol. Donepezil had only marginally enhanced potential to induce catatonia which was statistically insignificant (p>0.05).
Inducing psychosis in animals with methylphenidate is successful, and donepezil appears to have promise as an adjunctive treatment for antipsychotics.

Study of IDH1 (R132H) Mutation and Expression of ATRX Marker in Correlation with the Histopathological Grading in Gliomas

Pooja Jha, Samarth Shukla, Sunita Vagha, Ravindra P. Kadu, Sourya Acharya

Challenges and Advances in Pharmaceutical Research Vol. 6, 29 August 2022, Page 114-125

Background: The third highest cancer associated mortality and morbidity rates are associated with primary malignant brain tumors among lives worldwide. Newer WHO CNS tumor classification shows that mutation of IDH1 is also a predictive factor. The presence of IDH1 alteration results in an increased progression free survival in gliomas. Similarly, ATRX mutations are associated with favorable outcome in astrocytic tumors. The present study makes an attempt to assess the correlation between IDH1 mutation and ATRX expression and histopathological grading in glial tumors which helps us to grade glial tumors in comparison with present day molecular advancements in a better way.
Objectives: To develop an understanding of the relationship between IDH1 and ATRX expression with the histopathological grades of glial tumors on immunohistochemistry.
Methods: The present study is an observational, analytical and retrospective study to be conducted for a duration of two years, in the Histopathology and Immunohistochemistry division of the Pathology Department, Jawaharlal Nehru Medical College, Sawangi (Meghe), in coordination with the Department of Neurosurgery, Acharya Vinoba Bhave Rural Hospital, Sawangi (Meghe). In this study, approximately 45-50 resected specimens from suspected cases of Glial tumours received in the Department of General Pathology, J.N.M.C. will be taken. We will evaluate the correlation between IDH1 mutation and ATRX expression with the histopathological grades in glial tumors in comparison with the present-day molecular advances on immunohistochemistry for better understanding through a well-tabulated master chart.
Results: The observations will be depicted in a well-tabulated master chart.
Conclusion: Conclusion will be elicited from the results procured from the research.

Mechanisms of Antimicrobial Resistance in Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)

Mohamed Raslan, M. S. Eslam, A. R. Sara, Nagwa A. Sabri

Challenges and Advances in Pharmaceutical Research Vol. 6, 29 August 2022, Page 126-148

Antibiotics are widely employed as a medicinal drug in the treatment of several infectious diseases. Antimicrobial resistance has been linked to high death rates, increasing healthcare economic expenses, and decreased productivity. The chapter aimed to highlight on the current mechanisms and causes of antimicrobial resistance in severe acute respiratory syndrome soronavirus-2 (SARS-CoV-2). Antibiotic misuse and other social influences are major contributors to the emergence of antibiotic-resistant bacteria. Investigations revealed that healthcare systems are using antibiotics to treat all SARS-CoV-2 infections, even if the symptoms are mild, despite the fact that only 10% to 15% of infected SARS-CoV-2 cases had secondary bacterial infection. Furthermore, overburdened healthcare systems, lack of proper infection control measures, and increased production of personal protective equipment (PPE) all are exacerbating the emergence of antibiotic resistance. Emerging genetic variants of COVID-19 showed to diminish the efficacy of different COVID-19 vaccines, indicating the need for periodical vaccination boosters. Antibiotic stewardship should be promoted in health care facilities with proper flexibility when need.

Elemental Analysis of Leaves and Stem Barks Powder of Woodfordia fruticosa

Neeli Rose Beck

Challenges and Advances in Pharmaceutical Research Vol. 6, 29 August 2022, Page 149-156

This chapter aims to investigate essential and trace elements of leaves and stem barks of Woodfordia fruticosa. The phytoconstituents of herbal medicinal plants and the number of trace elements play an important role in the body as curative and preventive agents for combating diseases, nutritive and catalytic disorders. Even at low concentration, the toxic effects of metals are damaging to the human body and all living organisms. It is a necessary step in identifying components and their concentrations in herbal and food products. The current study gives information on the availability of various critical minerals and phytoconstituents that can be used to provide dietary elements and may also aid in the development of new medication formulations.