Prof. Vinoth Prabhu Veeramani
University of Tabuk, Kingdom of Saudi Arabia.

ISBN 978-81-969009-4-6 (Print)
ISBN 978-81-969009-7-7 (eBook)
DOI: 10.9734/bpi/acpr/v4

This book covers key areas of pharmaceutical research. The contributions by the authors include diabetes mellitus, lipid profile, anthropometric parameters, habitual consumption, solid dosage form, drug administration, orally dissolving tablet, oral cavity, nanoparticle, secondary metabolites, agro-waste, animal proteins, macronutrients, diabetic nephropathy, autoimmune destruction, peripheral neuropathy, insulin resistance, fluoride toxicity, glomerular filtration, dental fluorosis, hormonal imbalance, polycystic ovary syndrome, phytochemical analysis, signaling molecules, metabolic disorders, glucose stimulation, Biomaterials, tissue engineering, bone regeneration, 3-D and 4-D bioprinting, macrophages, hepatoprotective activity, hepatotoxicity, liver disease, ayurvedic treatment, pharmacovigilance, AYUSH drugs, adverse drug reactions, traditional medicine, ASU medications, mouth dissolving tablets, angiotensin-converting enzyme, silver nanoparticles, one pot synthesis, organic surfactants, colorimetric sensors, cytoblastin, antitumor properties, vinka alkaloids, synthetic molecules, biological fluids, nanoparticle, radiosensitization, microdosimetry, theory of dual radiation action, Auger electron, Monte Carlo simulation, proximity function, relative biological effectiveness. This book contains various materials suitable for students, researchers and academicians in the field of pharmaceutical research.


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The primary objective of the chapter is to identify the effects of Vitex agnes castus on hormonal imbalances in Polycystic Ovary Syndrome. Women are now commonly suffering from polycystic ovary syndrome. Among the entire population, only 6-8% of the women can identify this issue in their reproductive age. The primary causes of this issue include the problem in the level of female sex hormones and higher levels of androgens, the male hormones. In this study, the albino rats were treated with 8mg of estradiol valerate to induce their PCOS level. Additionally, it investigated the levels of luteinizing hormone, follicle-stimulating hormone, testosterone, dehydroepiandrosterone sulphate, Estradiol, Progesterone, and Prolaction. In this chapter, the increased levels of estradiol and decreased level of progesterone results in failure of ovulation which is one of the notable features of infertility have been explored. On the other hand, these altered levels are reversed in rats treated with vitex agnus castus fruit extract for the normalization of progesterone concentrations. Several groups have also demonstrated that vitex agnus castus extracts bind to the estrogen receptor and have weak estragenic effects, suggesting that chasteberry may also affect the estrogen/progesterone balance.

The final conclusion stated that PCOS is highly impacted by the levels of hormones and vitex agnus castus can generate the reverse adverse effects of hormonal imbalance for PCOS individuals.

This chapter highlights the Hepatoprotective potential of ethanolic extract from Stems of Anisochilus carnosus against carbon tetrachloride induced toxicity in rat. An ethanolic extract of stems of Anisochilus carnosus (EEAC) was studied for hepatoprotective activity against carbon tetrachloride (CCl4) induced hepatotoxicity in rats. Fresh stems were collected from Sri Venkateswara University campus, India. The plant material was dried under shade at room temperature, reduced to moderately coarse powder and extracted successively with 95% ethanol using soxhlet apparatus.

Hepatotoxicity was induced in Albino wistar rats of either sex by intraperitoneal injection of CCl4 [CCl4 in olive oil 1:1]. Ethanolic extract of Anisochilus carnosus was administered to the experimental rats at two dose levels 200 and 400mg/kg body weight. The hepatoprotective effect of the extract was evaluated by the assay of liver function biochemical parameters like Serum Glutamate Pyruvate Transaminase (SGPT), Serum Glutamate Oxaloacetate Transaminase (SGOT), Alkaline Phosphatase (ALP), Total Bilirubin and Total Protein. In ethanolic extract treated animals, the toxic effect of CCl4 was controlled significantly as compared to the normal and the standard drug silymarin treated group. CCl4 is one of the most commonly used hepatotoxin in the experimental study of liver diseases. The lipid peroxidative degeneration of bio membranes is one of the major causes of hepatotoxicity of CCl4. The increase in the levels of serum bilirubin reflected the depth of jaundice and the increase in transaminases and alkaline phosphate were the clear indication of the cellular leakage and loss of functional integrity of the cell membrane. Finally, it is concluded that the ethanolic extract of stems of Anisochilus carnosus possess hepatoprotective activities more or less depending on the dose levels.

This chapter aims to investigate the Effect of habitual consumption of Madhuca longifolia drinks on diabetes and dyslipidemia among santhal tribals. Madhuca longifolia (mahua) is a tropical tree widespread throughout India, primarily on plains.  Because of its numerous therapeutic benefits, the tree is seen as a godsend by tribals who live in the forest.  Further studies proved that beneficial effects are observed in Santhals many of whom are regular consumers of Madhuca longifolia drinks. The authors also did a study on this aspect.

Diabetes and lipid profiles of blood, as well as conventional anthropometric parameters, were assessed in a Santhal tribe population (only males were recruited), many of whom, but not all, are habitual mahua drink consumers. The results were statistically analyzed and compared using the student's t-test, and conclusions were reached.

The results demonstrate that anthropometric measures do not differ much, but FBS does. HbA1c, cholesterol, and LDL cholesterol levels are reduced among mahua consumers compared to non-consumers. When compared to the other group, mahua consumers have higher HDL levels. In the case of VLDL and triglycerides, no significant effect was detected.

The research found that regular mahua drinks among the Santhal tribe improved diabetes and lipid profiles, with the exception of triglycerides and VLDL.  More extensive research is required to get accurate insight and practical benefits in this regard.

Insights into the Role of Preptin in Diabetes

K. A. Arul Senghor, V. M. Vinodhni, P. Renuka, S. Rooban

Advanced Concepts in Pharmaceutical Research Vol. 4, 1 January 2024, Page 30-40

Peptide hormones are a category of signaling molecules that consist of amino acids and are synthesized and secreted by several endocrine glands distributed across the human body. Numerous physiological functions, including development, metabolism, reproduction, and stress response, are regulated by these hormones. Preptin is a recently identified peptide hormone synthesized within the pancreas, predominantly by the beta cells. This hormone is a constituent of a broader hormone family that includes insulin, amylin, and pramlintide. Preptin seems to be primarily involved in amplifying the actions of insulin. Type 2 diabetes is characterized by insulin resistance. We could find out how preptin and type 2 diabetes interact, leading to novel treatments and prevention methods.

The purpose of the present work was to mask the taste of Ambroxol hydrochloride and to formulate its patient- friendly dosage form. Solid dosage forms also present significant administration challenges in children, mentally challenged and uncooperative patients. Moreover, patients travelling with little or no access to water, limit utility to orally administered conventional tablets or capsules. Complexation technique using KYRON -T-114 an ion-exchange resin was used to mask the bitter taste and the drug loading onto the ion-exchange resin was optimized for ratio of drug to resin, effect of pH and effect on soaking time. The resinate was evaluated for taste masking and characterized by FT-IR and DSC. Then the taste-masked drug was formulated into a fast dissolving tablet (FDT). FT-IR spectroscopy was employed to ascertain the compatibility between Ambroxol, hydrochloride and the selected polymers. The pure drug and drug with excipient were scanned separately. The developed tablets were evaluated for hardness, friability, drug content, weight variation, content uniformity, friability, water absorption ratio, in-vitro disintegration time and in-vitro drug release studies.IR and DSC spectra revealed that there were no possible interactions between the drug and polymer. Maximum loading was obtained at drug–resin ratio 1:2, pH 7, and soaking time 30 min. A successful taste masking of resinate was confirmed by time intensity method. The values of pre- compression parameters evaluated and were within prescribed limits and indicated good free flowing properties. The data obtained of post-compression parameters found superior over conventional formulation. The F3 batch with disintegration time 30.4±0.64 sec and dissolution 98.4±2.69 was selected as optimized formulation, this was compared with conventional marketed formulation and was found superior. The data obtained of post-compression parameters such as weight variation, hardness, friability, wetting time, water absorption ratio, content uniformity, disintegration time and dissolution and was found superior over conventional formulation. The obtained results revealed that Ambroxol hydrochloride has been successfully taste masked and formulated into an FDT as a suitable alternative to the conventional tablets.

Estimation and Comparative Overview of Serum Fluoride and Renal Parameters in Diabetic Nephropathy

Mohan Krishna, Munilakshmi U., Saideepika R., Shashidhar K. N., Bhuneswar Yadav

Advanced Concepts in Pharmaceutical Research Vol. 4, 1 January 2024, Page 52-67

This study estimate and compare Blood Glucose and Fluoride levels within study groups and to correlate serum renal parameters with fluoride among study subjects. Diabetes mellitus (DM) and its microvascular complication; diabetic nephropathy (DN) is documented as a more prevalent disorder in fluoride endemic areas across the world. Kidneys are the major route of excretion of fluoride and are thus the primary organ affected. Fluoride in minor quantities may also be excreted through sweat, saliva and feaces. Though Fluoride in minor quantities (<1.5 ppm) is considered to be essential for dental and bone enamel mineralization which form fluroapetite. Chronic exposure (> 2ppm) is considered to be toxic leading to fluorosis. This study was conducted at Sri R.L. Jalappa Hospital attached to Sri Devaraj Urs Medical College, Constituent of Sri Devaraj Urs Academy of Higher Education and Research, Karnataka, India. Total 90 subjects with the age group 45-75 years of either gender were included. Our results showed that Fasting, post prandial blood glucose values and serum Fluoride were significantly higher (x%;179.27±53.86, 148±41.96,236.50±64.83, 250.43±72.85, 0.63±0.59, 0.52±0.3 p<0.001) in T2DM without CKD group as compared to the controls and T2DM with CKD. Renal profile when compared between three groups Urea, Creatinine and Potassium were significantly higher in T2DM with CKD as compared to controls and T2DM without CKD. We conclude that analysis of serum/ urine fluoride can be preferred for the subjects attending medicine OPD who are at risk, Installing water defluroditation plants at every village as they and livestock are mainly exposed to fluoride, Creating awareness among residents by conducting regular camps and routine medical checkups and Estimate fluoride levels of potable water at regular intervals, which would help decrease its effect among living system. This study also supports the hypothesis of increase serum Fluoride increases DM and DN which is evident from the results as we observed significant increase of serum fluoride in T2DM and DN subject comparecto controls. Evaluation of these parameters may help in early diagnosis and management and may help better patient care and nation as well.

A Comprehensive Review of 3D and 4D Bioprinting Techniques and Biomaterials for Bone Regeneration Applications

Gurdev Preet Singh, Kanika Chandel, K. J. Singh

Advanced Concepts in Pharmaceutical Research Vol. 4, 1 January 2024, Page 68-86

Material Science, Medicine and Chemistry are research fields that turn us towards the field of biomaterials and tissue engineering. The making of biomaterials for drug delivery, tissue engineering and other medical diagnostics is basically planted on chemistry. Moreover, the physical and chemical properties of materials can also balance the biological responses. In this article, we report the evolution of biomaterials with time, their types and their use in bone tissue engineering. Various polymers which are attractive biomaterials for their potential in biomedical applications have been discussed. Authors have also conversed about 3D Printing as a technology and the whole process of bioprinting. Fore coming biomaterials which can be used for 3D bioprinting and what are the conditions of such materials have also been discussed in brief. Future perspectives on biomaterials, 3D and 4D bio- printing are also mentioned.

Morinda citrifolia commonly called as Noni belongs to Rubiaceae family was used for synthesis of Ag and ZnO nanoparticles using green synthesis method. Morinda citrifolia (Noni) fruit juice is used as medicine for several diseases such as arthritis, diabetics, high blood pressure, muscle aches and pains, menstrual problems, headaches, heart diseases, AIDS, cancer, gastric ulcers, sprains, mental depression, senility, poor digestion, atherosclerosis, blood vessel problems and drug addiction. Noni has unique medicinal properties which help in normalization of abnormally functioning cells by delivering the bio-chemical nutrients. Noni fresh fruits obtained from the trees present in the campus of GITAM, Visakhapatnam, India. Synthesized Ag and ZnO nanoparticles have been applied on to jean fabric by dip and cure method. Nanoparticles were characterized by different methods such as UV- VISIBLE, FTIR, SEM, EDS, TEM and a comparative study of antimicrobial activity were done. The development of colour change in the nanoparticles was confirmed by UV – Spectroscopy. Identification of functional groups in fruit which was responsible for reduction of nanoparticles was observed by FTIR analysis. The size and morphology of the nanoparticles were observed by SEM and TEM. The presence of elemental silver and zinc were confirmed by EDS. The silver and zinc oxide nanoparticles synthesized using Noni fruit extract exhibited great inhibition against bacterial pathogens. Application of Ag and ZnO nanoparticles to jean fabric may reduce bacterial infections and blocks UV rays. Zone of inhibition of silver was almost similar to zinc oxide nanoparticles but comparative to silver, zinc oxide was cost effective and less toxic.

Pharmacovigilance Practice in AYUSH Drugs: Present Status and Future Prospective

M. G. Rajanandh, D. Chamundeeswari

Advanced Concepts in Pharmaceutical Research Vol. 4, 1 January 2024, Page 100-105

This chapter focuses on requirement of Pharmacovigilance in AYUSH Drugs. Since centuries Ayurveda and other traditional systems of medicine are practised in this continent. They are regarded as the safest medical systems. However with the scientific ethos everything is rejected or accepted in the light of available clinical data only. Hence, to create pharmacovigilance, program for AYUSH drugs become essential for giving them credibility. Quality of the ASU drugs may be hampered by poor quality raw material, plant preparations and not prepared following specific procedures. Good dispensing practices ensure that an effective form of the correct medicine is delivered to the right patient, in the correct dosage and quantity, with clear instructions, and in a package that maintains the potency of the medicine. Clinical use should be regulated by adopting Good Clinical Practice of ASU system to avoid the Adverse drug Reactions. Cooperation and sharing of information among the related drug regulating agencies should also be promoted.

Objective: The aim of this study was preparing once daily mouth disintegrating tablets to handle easily for adult hypertensive patients who have difficulty in swallowing.

Background: The oral bioavailability of Imidapril can be enhanced by decreasing its extent of first pass effect. Mouth dissolving tablet formulation has been widely and successfully applied to improve the dissolution, solubility, and consequently the bioavailability of poorly water-soluble drugs.

Methods: Imidapril mouth dissolving tablets (MDTs) were prepared by direct compression method using different concentrations of synthetic super disintegrants namely Sodium starch glycolate, Croscarmellose sodium & Kyron T-314. The prepared tablets were evaluated for weight variation, thickness, hardness, friability, content uniformity, disintegration time and In-vitro dissolution studies.

Results: The micropolitics study indicates that all formulations were of acceptable to good flowability. Tablet hardness and friability indicated that the prepared formulations were having good mechanical strength. The most satisfactory formulation F5 containing Sodium starch glycolate showed minimum disintegration time of 19 s and released a maximum amount of drug in 30 min in phosphate buffer 6.8pH, by an appropriate combination of excipients. The optimized F5 formulation containing Sodium starch glycolate was found to be stable during stability studies conducted for 3 mo as per International Conference on Harmonization (ICH) guidelines. The dissolution rate was found to be increased linearly with increase in the concentration of super disintegrant. The investigated super disintegrants can be ranked based on the overall in-vitro release profile of Imidapril Mouth dissolving tablet i.e. Sodium starch glycolate>Kyron T314>Croscarmellose sodium.

Conclusion: The present study conclusively proved that Imidapril MDTs could be successfully developed using various super disintegrants. The prepared tablets gave promising results with respect to the faster release of Imidapril. Further clinical studies are suggested to confirm the ability of the best-achieved system to avoid the first pass metabolism of Imidapril and improve patient compliance.

This chapter outlines a streamlined one-pot synthetic approach for producing silver nanoparticles silver nanoparticles capped with tartaric acid while maintaining a controlled size. Comprehensive characterization using UV/Vis and FTIR spectroscopy, SEM, DLS, and Zetasizer techniques was conducted to unveil key properties of the nanoparticles. The observation of a Surface Plasmon Resonance (SPR) band at 406 nm with 1.07 absorbance units confirmed successful synthesis. SEM images illustrated well-dispersed, spherical particles, and the z-average size distribution in colloidal solution was determined to be 79.20 nm, with a surface charge of -28.2 mV. The antibacterial efficacy of the capped nanoparticles, both independently and in conjunction with fluoroquinolones (Ofloxacin, Sparfloxacin, Ciprofloxacin, and Gemifloxacin) and macrolides (Erythromycin and Azithromycin), were assessed against gram-negative and gram-positive organisms using the disc diffusion method. Antioxidant activity against the DPPH (1, 1-Diphenyl-2-picrylhydrazyl) was also evaluated by the standard assay method. Positive synergistic effects were noted, enhancing the antibacterial activity of antibiotics against studied microorganisms. The study suggests the potential therapeutic application of Tartaric acid-capped silver nanoparticles in combination with antibiotics. Additionally, the capped nanoparticles exhibited noteworthy antioxidant activity, indicating their versatility in biomedical sciences applications.

Estimation of Vinblastine in Pharmaceutical Formulations by RP-HPLC Method

P. Rama Krishna Veni, N. Sharmila, B. Hari Babu

Advanced Concepts in Pharmaceutical Research Vol. 4, 1 January 2024, Page 140-152

Vinblastine, a Vinka alkaloid and a chemical analogue of vincristine is generally used in combination therapy with synthetic molecules. A new simple, precise and accurate reverse phase HPLC method was developed and validated for the estimation of vinblastine in pharmaceutical formulations using the mobile phase 90% methanol, 5% acetonitrile and 5% of 0.1% orthophosphoric acid and the pH was maintained at 3.5. Analysis was carried out using PEAK 7000 isocratic HPLC with rheodyne manual sample injector with a switch (77251). The resultant chromatogram obtained has a high resolution and low tailing factor (1.29). The linearity curve showed a correlation coefficient (r2) of 0.999 for a wide range of drug concentrations of 3-15 ppm. The method was also validated in respect of precision, accuracy and specificity. The applicability of the method was also tested with commercial sample of Cytoblastin. This method is more accurate, precise and convenient in terms of linearity, accuracy, precision, and others.

Background: Auger cascades generated in high atomic number nanoparticles (NPs) following an ionization were considered as a potential mechanism for the NP radiosensitization. The Auger electrons have short ranges and can locally damage tumor cells, resulting in larger biological effect than radiation alone.
Aim: In this work, we investigated the microdosimetric consequences of the Auger cascade using the theory of dual radiation action (TDRA) and proposed a novel Bomb model as a general framework for describing NP-related radiosensitization. When triggered by an ionization event, the Bomb model considers the NPs that are close to a radiation sensitive cellular target generate dense secondary electrons and kill the cell according to a probability distribution, acting like a "bomb".
Methods: TDRA plus a distance model was used as the theoretical basis for calculating the change in \(\alpha\) of the linear-quadratic survival model and the relative biological effectiveness (RBE). In TDRA, cellular lesions are assumed to be formed as a result of the combination of pairs of sublesions (e.g., chromosome break) in the sensitive sites of the cell. In addition, the yield of sublesions formed within spherical sites is assumed to be proportional to the energy deposited to the site. We calculated the quantities for SQ20B and Hela human cancer cells under 250kVp x-ray irradiation with the presence of gadolinium-based NPs (AGuIXTM), and 220kVp x-ray irradiation with the presence of 50 nm Gold NPs (AuNPs), respectively, and compared with existing experimental data. Geant4 based Monte Carlo (MC) simulations were used to (1) generate the electron spectrum and the phase space data of photons entering the NPs and to (2) calculate the proximity functions and other related parameters for the TDRA and the Bomb model.
Results: The Auger cascade electrons have greater proximity function than photoelectric and Compton electrons in water by up to 30%, but the resulting increases in \(\alpha\) are smaller than those derived from experimental data. The calculated RBEs cannot explain the experimental findings. The relative increase in \(\alpha\) predicted by TDRA is lower than the experimental result by a factor of at least 45 for SQ20B cells with AGuIX under 250kVp x-ray irradiation; and at least 4 for Hela cells with AuNPs under 220kVp x-ray irradiation. The application of the Bomb model to Hela cells with AuNPs under 220kVp x-ray irradiation indicated that a single ionization event in NPs caused by higher energy photons has a greater probability of killing a cell. NPs that are closer to the cell nucleus are more effective for radiosensitization. The comparison of Hela cell with AuNPs irradiated with photons of different energy implies that NP ionization by photon of higher energies have higher killing power, and the Compton scattering in NP may have a stronger effect than photoelectric effect, even though the latter can result in Auger cascade.
Conclusion: Microdosimetric calculations of the RBE for cell death of the Auger electron cascade cannot explain the experimentally observed radiosensitization by AGuIX or AuNP, while the proposed Bomb model can be a potential candidate for describing NP-related radiosensitization at low NP concentrations.