Prof. Randa Salah Gomaa Mahmoud
University of Zagazig, Egypt.

Short Biosketch

ISBN 978-81-975317-5-0 (Print)
ISBN 978-81-975317-2-9 (eBook)
DOI: https://doi.org/10.9734/bpi/prrat/v3

This book covers key areas of pharmaceutical research. The contributions by the authors include nanoemulgel, skin aging, protein modification, DNA damage response, necrotic cell death, antiepileptic drugs, epilepsy, clinical diagnosis, interictal epileptiform discharge, duloxetine, diabetic peripheral neuropathy, major depressive disorder, generalized anxiety disorder, new drug application, active pharmaceutical ingredient, organic and inorganic impurities, permitted daily exposure, solvatomorphism, toxic impurities, antidiabetic drugs, emulsomes, lipophilic drug delivery, cationic surfactants, generic drugs, proton pump inhibitors, good laboratory practices, chemistry manufacturing, and controls, post-surgical septicemia, free triiodothyronine, thyroid dysfunction, SOFA score, prodrug approach, parkinson's disease therapy, dopamine, blood-brain barrier, prodrug l-dopa, drug discovery, cancer genomics, post-translational modifications, biomarkers, high-throughput screening, urolithiasis, anti-urolithiatic activity, renal stones, Impurity Profiling, Antidiabetic Drugs, Active Pharmaceutical Ingredient, Oral Antidiabetic Drugs. This book contains various materials suitable for students, researchers, and academicians in the field of pharmaceutical research.


Effects of Long-term Antiepileptic Drugs (AED) on Serum Copper Level in Children with Epilepsy

Md. Ranzu Ahmed, Israt Jahan, Shamim-Ara-Sarkar, Habibur Rahman, Mohammad Jahangir Alam Sarker, Faridul Alam

Pharmaceutical Research - Recent Advances and Trends Vol. 3, 21 June 2024, Page 1-13

Background: Epilepsy is a central nervous system disorder in which brain activity becomes irregular, causing seizures or periods of unusual behavior, sensations, and sometimes loss of awareness. Serum copper level may change due to long-term use of antiepileptic drugs. Epilepsy is one of the most common neurological diseases with a prevalence rate varying from 2.8 to 19.5 per 1000 general population and it prevails more especially among school children.

Objective: The purpose of the present study was to assess the serum copper level in childhood epilepsy treated with long-term Anti-Epileptic drugs (AED).

Methodology: This cross-sectional study was carried out in the Department of Pediatric Neurology, Bangabandhu Sheikh Mujib Medical University (BSMMU) from March to August 2013. The sample size was one hundred, among these fifty were case (epileptic children who had received anti-epileptic drugs (Carbamazepine and/or Valproic acid) for more than three months) and the rest fifty were control (newly diagnosed epileptic children, who had yet not received antiepileptic drug). Serum copper (Cu) was measured by atomic absorption spectrophotometer. After collecting all the data, analysis has been done by using SPSS and the results are displayed in tables and diagrams.

Results: The mean copper level was 1.11±0.32 µg/ml in case group and 0.96±0.20 µg/ml in the control group, which was statistically significant (p<0.05). In this study, epileptic group had a 34% family history of epilepsy, while in control group it was 16% and that was statistically significant (p<0.05).

This study also indicated that 78% generalized tonic clonic seizures were in the epileptic group and 70% were in the control group. Serum levels of copper in patients with epilepsy on treatment (particularly with sodium valproate and carbamazepine) were high.

Conclusion: The use of one drug or multiple drugs in the treatment of epileptic patients may play a significant role in increasing copper serum levels.

Nanoemulgel as an Efficacious Tool for the Aging Process

Mitali Singh, Zaira Hussain, Aafreen

Pharmaceutical Research - Recent Advances and Trends Vol. 3, 21 June 2024, Page 14-39

Becoming older is complicated and influenced by internal and external factors. A loss follows it in both the function and look of the skin as it progresses. One must look to cutting-edge approaches within the pharmaceutical and dermatological research communities to solve this complex challenge. The function of nanoemulgels as a potent weapon in the battle against skin ageing is thoroughly examined in this article. To develop effective treatments, it is essential to have an understanding of the processes that result in the ageing of the skin. The interaction of external factors like pollution, UV radiation, and lifestyle choices with intrinsic ones like biological processes and inheritance accelerates ageing. Nanoemulgels offer a better platform for accurately and successfully delivering anti-aging drugs due to the unique features that they possess. Utilizing nanoemulgels is the most current innovation in the fight against the signs of ageing skin that have been discovered. This article presents a comprehensive examination of their workings, including their benefits and limitations, the methods used to prepare them, and the variety of applications they find use in. Nanoemulgels show significant promise as a potential solution to the challenging issue of aging because of their capacity to deliver individualized treatments that are also very successful in preserving a youthful and healthy appearance of the skin.

Generic Drugs: The Evolving Landscape and the Mentalities

Francois-Xavier Lacasse

Pharmaceutical Research - Recent Advances and Trends Vol. 3, 21 June 2024, Page 40-45

The present study discusses the expense associated with development, by narrowing the cost of development (raw materials) and workforce for generic drugs. During the last decade, the generic landscape has considerably evolved. The last two waves of several MM$ of off-patented drugs may be held responsible for this change. For example, the amount of money generated by statins, the proton pump inhibitors (PPIs), according to several experts, may now be difficult to reproduce. However, things cannot be seen from a monolithic way of thinking but should be foreseen with a holistic approach. The cost of generic medications is continuously declining. It is paradoxical because government organizations are raising their expectations for quality at the same time, driving up the cost of development.  Furthermore, in December 2016, the FDA released revision 2 [1] of their Refuse to Receive Standards, for ANDA Submissions. After discussion with several experts who have attended numerous meetings on the topic with the FDA, data quality and regulatory operations were at the heart of this new guidance. Additionally, the generic market is facing the challenge that it will have to change its vision if it wants to survive, biologics getting more and more popular and cannot be “genericized” per se, but will become biosimilar, or second-entry biologics. This assumption is confirmed by looking at the contract research organization where the number of bioequivalence studies has been going down over the last decade. Therefore, generics will have to think outside of the box, and to date, the best compromise seems to develop new routes of administration and or new formulations of an already marketed drug substance. This short communication will illustrate a way of thinking and a summary of the generic landscape that is evolving.

Emulsomes: A Promising Tool for Lipophilic Drug Delivery

Dipti Gohil, Nirmal Shah, Sunil Kardani, Kinjal Patel, Shivkant Patel, Rajesh A. Maheshwari, Piyush Sadhu, Mamta Kumari, Niyati Shah

Pharmaceutical Research - Recent Advances and Trends Vol. 3, 21 June 2024, Page 46-56

Emulsomes, which are lipid-based nanocarriers, combine the advantages of liposomes and emulsions, providing a versatile platform for the encapsulation and controlled release of hydrophobic drugs. This chapter provides a comprehensive overview of the structural characteristics, preparation methods, and functional properties of emulsomes, highlighting their role in overcoming the challenges associated with the delivery of poorly water-soluble drugs. Key topics include the physicochemical properties of emulsomes, such as their size, stability, and drug-loading capacity, which are crucial for their effectiveness in drug delivery. The chapter details various preparation techniques, including high-pressure homogenization and solvent evaporation methods, and discusses how these techniques influence the characteristics and performance of emulsomes. The potential applications of emulsomes in improving the bioavailability and therapeutic efficacy of lipophilic drugs are thoroughly examined. Case studies and experimental data are presented to illustrate the successful use of emulsomes in delivering anticancer agents, antifungal drugs, and other therapeutic compounds. Additionally, the chapter delves into the mechanisms of drug release from emulsomes and the factors that affect their in vivo behavior, such as particle size and surface modifications. Safety, biocompatibility, and regulatory considerations are also addressed, emphasizing the importance of thorough preclinical and clinical evaluations to ensure the safe use of emulsomes in medical applications. Finally, the chapter discusses future directions in emulsome research, including the development of multifunctional emulsomes and their potential use in personalized medicine.

Pharmacological Aspects of Duloxetine: An Update

Deepak P., Kumar T. N.

Pharmaceutical Research - Recent Advances and Trends Vol. 3, 21 June 2024, Page 57-66

Duloxetine is thought to block the reuptake of serotonin and norepinephrine in Onuf's nucleus in the sacral spinal cord, thereby activating pudendal motor neurons that increase the urethral striated muscle tone and the force of sphincter contraction. Duloxetine was developed for the management of depression. This drug was later found to be effective in the treatment of Stress Urinary Incontinence. It works by preventing serotonin and norepinephrine from being reabsorbed in a region of the sacral spinal cord where these neurotransmitter receptors are highly concentrated. This stimulates particular motor neurons that control the urethral striated muscle sphincter.

Potential of Fruit Peel Extracts in Dissolving Simulated Renal Stones in In vitro Conditions

Karuna Sree Varicola, Amreen Siddiqua A., Keerthi Dintyala, Gandhi Ventrapati

Pharmaceutical Research - Recent Advances and Trends Vol. 3, 21 June 2024, Page 67-78

Objective: The present study evaluates the antiurolithiatic activity of selected fruit peels on simulated renal stones in in vitro conditions.

Background: Fruit peels are discarded in the majority of common fruits even though they are found to be safe for consumption. Fruit peels are rich in antioxidants and are the best source of rough dietary fiber. Apple peel possesses a high content of phenolic compounds which imparts anti-proliferative activity [1] and antioxidant activity.

Methods: Simulated renal stones were prepared by homogenous precipitation method. The criterion selected was to estimate the amount of calcium oxalate remaining in the semi-permeable membranes by Kramer and Tisdal method with slight modification. A suitable media was provided by the TRIS buffer.

Results: The crude methanol extract of Musa sapientum exhibited the highest dissolution of calcium oxalate ie.9.15 mg and the percent dissolved was found to be 91.5% in comparison to Malus pumila methanol extract which dissolved 8.96 mg (89.6%) and Punica granatum methanol extract which dissolved 8.0 mg (80.0%). Its activity was comparable with that of the standard drug Tamsulosin hydrochloride (400 mg) with a percentage dissolved of about 90.5%. The expected mechanism for the phytoconstituents present in the tested extracts in the management of urolithiasis includes diuretic, antispasmodic, and antioxidant activity, as well as an inhibitory effect on crystallization, nucleation, and aggregation of crystals.

Conclusion: Experimental evidence showed that methanol and aqueous fruit peel extracts of Musa sapientum, Malus pumila, and Punica granatum possess potential antiurolithiatic activity. Their effect is found to be significant and the extracts can be used in the treatment of lithiasis. Further, in vivo studies are needed to give a strong scientific basis for these in vitro findings.

Unveiling the Correlation Between Thyroid Dysfunction and Post-Surgical Septicemia in Geriatric Patients

Pallavi Rain, Jyoti Batra, Ankit Batra, Aarushi Batra

Pharmaceutical Research - Recent Advances and Trends Vol. 3, 21 June 2024, Page 79-99

Background and Aim: Sepsis is a life-threatening issue that happens when the body’s immune system has an extreme response to an infection, causing organ dysfunction. Critical illness and sepsis are difficult to treat with increasing age because of the poor adaptive physiological system as age progresses. The study tries to identify prognostic markers among thyroid hormones for post-surgical critically ill subjects, who have sepsis, to improve the outcome of patients with increasing age.

Methods: Post-surgical critically ill patients with sepsis were recruited in the study. Key features of the critically ill patient are severe respiratory, cardiovascular or neurological derangement, often in combination, reflected in abnormal physiological observations. Free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) were estimated by ARCHITECT immunoassay kits in 127 post-surgical critically ill patients with sepsis. Sequential Organ Failure Assessment (SOFA) score was recorded for each patient.

Results: The FT3, FT4 and TSH levels decreased and SOFA scores increased with increasing age. Thyroid markers were significantly inversely correlated with age (for FT4 r= -0.616, p<0.0001 and for TSH r= -0.453, p<0.0001), with the strongest correlation between FT3 and age (r=0.674, p<0.0001). A positive correlation was observed between SOFA score and age (r=0.577, p<0.0001). FT3 decreases SOFA and age increase from improved prognosis to worst prognosis (p<0.0001). The patients whose condition improved were mostly young as compared to the no change group, deteriorated group and expired group.

Conclusions: FT3 surfaced as a prominent prognostic marker that may be used in predicting the prognosis of post-surgical critically ill geriatric patients with sepsis.

Drug Discovery in Pharmaceutical Chemistry: An In-Depth Exploration

Shivkant Patel, Dillip Kumar Dash, Dipti Gohil, Ashim Kumar Sen, Dhanya B. Sen

Pharmaceutical Research - Recent Advances and Trends Vol. 3, 21 June 2024, Page 100-115

Drug discovery in pharmaceutical chemistry is a complex, multi-stage process aimed at identifying new compounds that can become effective therapeutic agents. This process involves several key phases: target identification and validation, hit identification, hit-to-lead development, lead optimization, preclinical development, and clinical development, culminating in regulatory approval. Each stage integrates diverse scientific disciplines and advanced technologies to ensure the discovery of viable drug candidates. Challenges such as high failure rates, complex disease biology, safety and toxicity concerns, and significant time and cost investments are inherent to this process. However, emerging trends like artificial intelligence, machine learning, personalized medicine, and the development of biologics and biosimilars are revolutionizing drug discovery, enhancing efficiency, and paving the way for more targeted and effective treatments. This exploration provides a detailed overview of each stage, highlights the associated challenges, and discusses the innovative trends that are shaping the future of pharmaceutical research.

Recent Advances in the Prodrug Approach to Parkinson's Disease Therapy

Donia Karaman, Fatma Haddad, Maryam Sawalha, Yahya Khawaja, Anas Najjar, Rafik Karaman

Pharmaceutical Research - Recent Advances and Trends Vol. 3, 21 June 2024, Page 116-140

Parkinson's disease is a neurodegenerative disorder that progresses aggressively and depletes the central nervous system of dopamine (DA). Dopamine replacement therapy has several issues, such as poor blood-brain barrier penetration and a progressive decline in treatment responsiveness. The primary components of this treatment are the initial prodrug L-dopa (LD) and actual dopamine. This chapter discusses prodrugs produced and generated chemically, such as amide, dimeric amide, carrier-mediated, peptide transport-mediated, cyclic, and enzyme-model prodrugs. The bioavailability of these kinds of prodrugs in animals was studied. A promising ester prodrug has been invented for intranasal delivery. LD methyl ester is currently in phase III clinical studies. Many amide prodrugs have been developed with better stability than ester prodrugs. Amide and dimeric amide prodrugs offer enhanced pharmacokinetics and greater blood-brain barrier (BBB) penetration. Linking LD to carbohydrates is one approach that draws advantages from the brain's glucose transport mechanisms. While there isn't a DA prodrug on the market at present, prodrugs seem to have a bright future in Parkinson's disease treatment. Prodrugs that contain LD ester, for instance, demonstrate promises in the intranasal delivery of LD, facilitating the absorption of therapeutic agents by the brain. Most DA prodrugs delivered by amide, cyclic, peptidyl, or chemical routes demonstrated better pharmacokinetic properties.

According to ICH Q3A(R), the impurity in a new drug substance is “any component of new drug substance that is not the chemical entity defined as new drug substance”. As Per ICH Q3B(R), the impurity in the new drug product is “any component of the drug product that is not the drug substance and excipients in the drug product.”

There are a number of spectroscopic methods that include Ultraviolet spectroscopy, Mass spectroscopy, Nuclear magnetic resonance spectroscopy and Chromatographic methods including HPLC, HPTLC, GC, and UPLC used for the identification and characterization of impurities in API and drug products. As well as hyphenated techniques like LC-MS, LC/ESI-MS, and LC-NMR-MS are used for impurity profiling of the drug. Forced degradation studies are used to facilitate the development of analytical methodology, to achieve a better understanding of drug substance and drug product stability, and to determine degradation pathways and degradation products. This study will help to get a stable formulation.

This review describes the number of impurities identified in the pharmaceutical drugs and the drug products used to treat type 2 diabetes. The impurities are classified according to ICHQ3A (R2) guidelines along with their identification. We delineate the impurity profiling of anti-diabetic drugs (Oral hypoglycemic agents) categories as Dipeptidyl peptidase-4 inhibitors, K-ATP channel blockers, Sulfonylureas, Alpha-Glucosidase inhibitors, Sodium-glucose co-transport-2 inhibitors, Biguanide and Thiazolidinedione.