Trends in Pharmaceutical Research and Development Vol. 1

For the first time, Simple, selective, sensitive RP-HPLC method developed for the separation and quantitative estimation of Levofloxacin (LEVO), Prulifloxacin (PRFX), Gatifloxacin (GATI), Sparfloxacin (SPAR), Moxifloxacin (MOXI) and Balofloxacin (BALO) relating to fluoroquinolone antibacterials in pharmaceutical dosage forms. The important advantage of the developed method was that the six separate drugs could be estimated on a single chromatographic system without modifications in detection wavelength and mobile phase by RP-HPLC. The chromatographic separation of the selected drugs carried out on Welchrom C₁₈ column consisting of 250 mm X4.6 mm, 5 µm particle size utilizing mixture of 10 mM phosphate buffer (pH 3.1): Acetonitrile in the ratio of 70:30,v/v as mobile phase at the flow rate of 1 mL/min with detection wavelength at 293 nm by using UV spectrophotometric detector with total run time of 10 minutes and 3.613, 4.230, 4.707, 5.497, 5.880 and 6.253 minutes of retention time, 12,261, 12,554, 13,157, 14,761, 14,912 and 15,916 of plate number, 1.106, 1.067, 1.040 and 1.073, 1.030 and 1.086 tailing factors were obtained for LEVO, PRFX, GATI, SPAR, MOXI and BALO respectively. All calibration curves for six drugs showed indicated linearity over a concentration range of 2-10 µg/mL. The results regarding to limit of detection (LOD) and limit of quantitation (LOQ) for LEVO, PRFX, GATI, SPAR, MOXI and BALO were found to be 0.116 µg/mL and 0.348 µg/mL; 0.152 µg/mL and 0.460 µg/mL; 0.084 µg/mL and 0.255 µg/mL; 0.186 µg/mL and 0.558 µg/mL, 0.162 and 0.493, 0.112 and 0.390 respectively. These results clearly show the low values of LOD and LOQ. The said proposed method utilized for quantification of the marketed formulation. The mean assay values for LEVO, PRFX, GATI, SPAR, MOXI and BALO arrived at 99.317±0.990%, 99.9±0.04%, 99.9±0.02%, 99.45±0.01%, 99.945±0.056% and 99.68±0.09% respectively.

Background: Myofascial pain syndrome (MPS) is a common pain condition characterized by a key symptoms and signs, determined by multiple etiologies, comorbid with a variety of systemic diseases and regional pain syndromes (RPS) and managed by diverse integrative therapies including complementary and alternative modalities (CAM) with variable outcomes.

Objective: This study aimed to concisely report 11 cases of myofascial pain syndrome managed by myofascial trigger point therapy.

Methods: The relevant information about 11 cases was collected prospectively using a semi-structured proforma. All patients were diagnosed mainly by detailed history and gold standard palpation method that helps identify taut muscles, tender myofascial trigger points, local twitch response and autonomic manifestations.

Results: Most of the patients with variable age and profession presented in emergency room with acute pain, limited motion, weakness, referred pain of specific pattern and associated autonomic signs and symptoms. Myofascial trigger point therapy alone with a timeline of about 30-60 minutes of 1-3 sessions brought about good results in all 11 patients (100%) who remained stable at two to three months follow-up. 

Conclusion: Myofascial pain syndrome linked with latent or active myofascial trigger points developed due to repeated strains and injuries needs to be diagnosed by history and palpation method, systemic evaluation and laboratory investigations. Though several interventions are used in myofascial pain syndrome, myofascial trigger point massage therapy alone is found to be reasonably effective with excellent results. This clinical case series is calling for double-blind randomized controlled trials among patients with myofascial pain syndrome not only in Saudi Arabia but also in other Middle East countries in future.  

The present study was undertaken to investigate the antioxidant and hepatoprotective effect of Spilanthes paniculata Wall. ex DC flower extracts against paracetamol-induced liver damage. The study was conducted in 36 male Wistar rats of either sex, and six groups were established. While the first group was maintained as normal control (NC, distilled water), Groups 2 to 6 were administered 3 g/kg Paracetamol (PAR) for 2 day, 100 mg/kg Silymarin (SMR), 500 mg/kg Methanolic extract (MESP), Petroleum ether extract (PEESP), Ethyl acetate extract of S. paniculata (EAESP) suspended in 0.5% tween 80 plus PAR, respectively. PAR was administered in the same schedule as in group 2, the treatment with silymarin and extracts was given for 10 days orally, respectively. It was observed that PAR significantly increased serum Alanine transaminase (ALT), Aspartate transaminase (AST), Alkaline phosphatase (ALP) activity liver MDA levels (P<0.01) and significantly decreased liver Glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) activity (P<0.01), when compared with the normal control group (NC). On the other hand, statistically significant (P<0.01) changes were observed in the biochemical parameters of the group which was administered SMR, PEESP and EAESP. Compared with the pathological changes observed in the liver in the form of congested sinusoids and centrilobular necrosis, in the group which was administered paracetamol alone (PAR), lesions were determined to be less severe particularly in the group (PEESP and EAESP). The study shows that administration of PEESP and EAESP offered a therapeutic potential for the treatment of hepatotoxicity induced by paracetamol via regulation of endogenous antioxidant system in liver.

Scientific and technical aspects as related to use of microorganisms in functional foods supplementation are highly diverse and complex, since they have to deal with the viability of microorganism’s strains as well as with the safe production, nutritional composition and acceptability of the new product. However, limited information is available on the microorganism’s (Lactic bacteria’s, Saccharomyces yeast, Kefir, Kombucha and Spirulina) which can be used in functional food supplements, as well as how to use these microorganisms and generation of foods of the future. This review reports detail this information. The data from this review can be useful to support for the development of new functional products, with microbial supplementation, to the market.

Aims: To review previous studies conducted on some Maltese medicinal plants for their immunomodulatory effects on lymphocytes.

Methodology: Human peripheral lymphocytes were obtained from the whole blood of human healthy volunteers. Several extracts were obtained from Olea europea L., Ephedra fragilis Desf., Aster squamatus (Sprengel) Hieron., Glebionis coronaria (L.) Tzvelev, Calendula arvensis L., Carlina involucrata Poir., Dittrichia viscosa (L.) Greuter, Galactites tomentosa Moench, Inula crithmoides L., Leontodon tuberosus L., Reichardia picroides (L.) Roth, Sonchus oleraceus L. and Ecballium elaterium (L.) A. Rich. These extracts, pure metabolites and phytohaemagglutinin were tested on both resting and stimulated lymphocytes. The blastogenic transformation was monitored by morphological observations and biochemical tests using the WST-1 tetrazolium reagent and the LDH cytotoxicity assay.

Results: This current study collates all previous studies. Most of the extracts tested exhibited lymphocyte activation, with the blastogenic transformation. Some extracts exhibited comparable activity to that of PHA. Metabolites showing such effects include oleuropein, ephedrine, cucurbitacin E and flavonoids. Extensive research on cucurbitacin E reveals that, in lymphocyte-cancer cell co-cultures, this metabolite induces lymphocyte activation, which in turn provokes cytotoxic effect on cancer cells.

Conclusion: The effects of extracts on the lymphocytes was exhibited by several extracts. In the case of oleuropein, ephedrine and cucurbitacin E, the relationship between structure and function can be deduced. However, the extracts from the Asteraceae family contained flavonoids, but no further chemical characterization was carried out. This review recommends further chemical characterization of the extracts and in depth analysis of the mechanisms for lymphocyte activation by plant metabolites. On the other hand, this study shows the potential use of these extracts to boost the immune system, alongside chemotherapeutic agents.

Since 2002, the folk medicine promotion and integration in the Congolese health’s system has become a reality because it has been proven to be a viable alternative for the majority of the population daily confronted to health problems due to the lack of access to primary care services.  Moreover, the cohabitation between the modern and folk medicine has been successfully implemented in many countries throughout the world and consequently, those countries are looked at a best examples of the integration of the folk medicine in their health’s system. As a result, a great number of the illnesses that torment people living in rural and urban areas are both cured by the modern physicians and traditional healers using different therapeutic approaches and schemes. The City of Lubumbashi in the DR Congo is also concerned this phenomenon and what precedes is raising the issue of ascertaining that the therapeutic implemented by traditional healers is valid.  Such a preoccupation is considered by the present survey which is interested in the evaluation of the antibacterial activity of three medicinal plants used in herbal medicine by the healers in the city of Lubumbashi. It is based on the ethnobotanical knowledge and the testing of sensitivity of the pathogen microbes towards the plant extracts of Terminalia mollis, Diospyros batocana and Antidesma venosum. Results from the testing of the plants extracts revealed that Proteus mirabilis is the microbe more sensitive to the extracts of T. mollis whereas Salmonellatyphii showed greater sensitivity to extracts of D. batocana and A. venosum. Concerning Klebsiella pneumoniae, no sensitivity was observed towards extracts of A. venosum. The extracts from T. mollis and D. batocana, tested against the reference bacteria, revealed to be bacteriostatic which behaviour justifies their use as sources of drugs against infectious illnesses by the healers in the City of Lubumbashi.

Aims: The study investigated the effect of ethanol extract of Xylopia aethiopica fruits on the histomorphology of the kidney of albino Wistar rats.

Study Design:  Twenty (20) albino Wistar rats weighing between 130–180 g were assigned into four (4) groups of five rats each. Group 1 served as the control group. Groups 2, 3 and 4 received orally, 250 mg, 500 mg and 750 mg of Xylopia aethiopica ethanol extract per kilogram body weight respectively for twenty-eight (28) days.

Place and Duration of Study: Department of Anatomy, Faculty of Basic Medical Sciences, University of Uyo, Akwa Ibom State, Nigeria.

Methodology: The body and kidney weights were observed and kidney was excised for histological studies using haematoxylin and eosin staining techniques.

Results: The final body and kidney weight showed significant weight increases in test groups compared with the control. The photomicrographs revealed gradual epithelial lining degeneration, vascular degeneration, inflammation and renal tubular degeneration and necrosis in the test groups when compared to the control group.

Conclusion: It can, therefore, be concluded that the administered doses of the extract of Xylopia aethiopica have nephrotoxic effects on the kidney of albino Wistar rats.

Datura innoxia indigenous shrub in South Asia region belongs to the family Solanaceae which contains medicinal important alkaloids (hyoscine, atropine, hycosamine, etc). Thirty adult rabbits of mixed breed, male and female were pretreated with 0.1 mg/500 mg of crude extract (1% of dimethyl sulfoxide (DMSO) solution) and injected 5 min later with 0.01 mg/500 mg of detomidine (group A, n=15) or Saline (group B, n=15). Mean arterial pressure, measurements and electrocardiography were performed for 65 min. After injecting crude extract of D. innoxia, the heart rate was increased by 45 and 46.34% in groups A and B, respectively. Heart rate remained increased after the injection of detomidine returning to base line values after 15 min. No increase in the mean arterial pressure (MAP) was noted in group B rabbits. Crude extract shortened PR and QT interval in both groups but after detomidine, PR and QT interval were enlarged significantly at the end of the experiment. The second degree atrioventricular was blocked in two rabbits after 40 min only in group B. It was concluded that alkaloid present in D. innoxia prevented detomidine induced Bradycardia  and might be useful during combination against the Bradycardia induced by alpha-2 agonist in the rabbits.

A simple, rapid and selective liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) is developed and validated for quantification of propranolol without the sample extraction step in rat plasma using tramadol as an internal standard (IS). The analytes are separated using an isocratic mobile phase which consist of methanol and 10 mm ammonium formate (70/30, v/v) on an isocratic UK-C18 (Imtakt Unison 2.0 × 50 mm, 3 μm) column and was analyzed by MS/MS in the multiple reaction monitoring (MRM) mode using the transitions of respective (M+H)⁺ ions, m/z 260.0→116.2 and m/z 264.2→58.2 for quantification of propranolol and IS, respectively. The standard calibration curves showed good linearity within the range of 2.0 to 800.0 ng/ml (r² = 0.999, 1/x² weight). The lower limit of quantification (LLOQ) was 2 ng/ml. The retention time of propranolol and IS were 1.12 and 0.939 min which means that it is the potential for the high-through put potential of the proposed method. In addition, no significant metabolic compounds were found to interfere with the analysis. Acceptable precision and accuracy were obtained for the concentrations over the standard curve range. The validated method was successfully applied for the pharmacokinetic studies after 2 mg/kg of propranolol HCl in the thioacetamide (TAA)-induced fibrotic rats.

Occupying only 0.01% of all adult cancer patients, the rare entity urachal adenocarcinoma constitutes 22-35% of adenocarcinomas originating from urinary bladder. Though with the gradual descend of the bladder in the course of development urachus should turn into median umbilical ligament, exceptional persistence of it can give rise to urachal cyst or urachal adenocarcinoma in adulthood. With only 43% of survival rate for 5 years and mean survival between 12 and 24 months urachal carcinoma is a devastating disease. Diagnosis of it is based on the MD Anderson Cancer Centre (MDACC) criteria. Computed Tomography (CT) Scan and/or Magnetic Resonance Imaging (MRI) Scan of abdomen and pelvis are the major imaging modalities to proceed towards diagnosis and staging. Not only histopathological examination but also immune-histochemical expression of both CK7 and CK20 suffice to clinch the diagnosis. Though surgical intervention forms the mainstay of treatment, several regimens of chemotherapy have also been tried to fight against unresectable, residual, extensive urachal carcinomas.

This case took place in a 52 years old male patient who was presented with a gradually enhancing infra-umbilical swelling with slow growing urinary symptoms. By dint of Ultrasonography (USG) and Contrast Enhanced CT (CECT) scan of whole abdomen the tumour was detected involving the bladder wall and the anterior abdominal wall. Cystoscopy was followed by upfront cytoreductive surgery. Histopathological examination revealed the diagnosis of an adenocarcinoma which was further confirmed to be an urachal remnant carcinoma with the help of immunohistochemistry. Post-operative CT scan showed residual disease involving bladder wall and was treated with an adjuvant platin based chemotherapy regimen.

Rhamnus prinoides finds therapeutic applications in traditional medicine in Southern Africa, which include treating pulmonary tuberculosis (TB), pneumonia, gonorrhoea, muscular rheumatism, cleaning the blood, bladder and kidneys. Hexane, chloroform, ethyl acetate and methanolic extracts from leaves and stem-bark of R. prinoides have been evaluated for their antioxidant activity by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay. The percentage values of radical of scavenging activity of these extracts have been found to be in the range of 03.33±0.89 to 59.55±2.27% at various concentrations. The IC₅₀ values of these extracts have been determined to be in the range of 710.50 to >3000 µg mL^-1. The positive control, ascorbic acid, showed an IC₅₀ value of <200 µg mL^-1. Additionally, all these extracts have also been evaluated for their inhibitory effect against six bacterial isolates viz. Escherichia coli (wild), Escherichia coli (H0157), Staphylococcus aureus, Listeria monocytogens, Pseudomonas spp. and Serratia marcescens and two fungal isolates viz. Penicillium digitatum and Candida albicans. The zones of inhibition have been found to be in the range of 8.8±3.0 to 15.8±1.4 mm diameter against bacterial isolates and 10.3±1.8 to 14.3±2.5 mm diameter against fungal isolates. The minimum inhibitory concentrations (MICs) of these extracts have been found to be in the range of <31.25 to > 1000 µg/mL. Further studies on this plant will be useful to commercialize products from this plant.

massively produced in mountainous regions Japan. Essential oil extraction was one of the effective approaches to overcome its issues. Materials from Crytomeric japonia, Lindera umbellata, Thujopsis dolabrata and Anise magnolia chips was applied for oil extraction by steam distillation and was chemically analyzed by Gas Chromatography. Preclinical studies of the essential oil were done with a support of the elderly commuting to the Day Care Service Center. Test room was created with the forest pictures, bird singing and water flowing sound as back ground music. Essential oil-flavored test was done to know the elderly preference using the questionnaire test.

The most favorite flavor by the elderly was Lindera umbellata due to make them refreshing. But they selected Thujopsis dolabrata flavor instead of Lindera umbellata, when changing the napkin. It implies that “Different flavor for Different situation”. Based on these results the flavored-napkin with anti-bacteria potency is a potential candidate to develop for the aged along with well-being and amenity life.

The present study was designed to investigate the role of combined administration of Ramipril and Candesartan against in vitro myocardial ischemic reperfusion injury in rat. Male Wistar albino rats were divided into five groups (= 6) and treated with saline (10 mL/kg), Ramipril (2 mg/kg), Candesartan (1 mg/kg), and the combination of both drugs, respectively 24 h before induction of global ischemia (5 min of stabilization, 9 min of global ischemia and 12 min of reflow). Combination of Ramipril and Candesartan when compared to the monotherapy significantly increased the levels of superoxide dismutase, reduced glutathione, catalase and nitric oxide and decreased the levels of thiobarbituric acid reactive substances. In addition, the superior protective role of combination of Ramipril and Candesartan on ischemia induced myocardial damage was further confirmed by well preserved myocardial tissue architecture in light microscopy and transmission electron microscopy analysis studies. The combination was proved to be effective in salvaging the myocardial tissue against ischemic reperfusion injury when compared to the monotherapy of individual drugs and further investigations on protective mechanism of drugs by increasing the nitric oxide level at molecular levels are needed.

Gastroretentive drug delivery system is the drug delivery system in which drug remains for a long span. In this review, we have discussed about factors affecting gastric retention and effervescent and non-effervescent drug delivery systems with the diagram in detail. It also includes in vitro evaluation techniques for evaluation of the performance of gastroretentive systems. Detail about mucoadhesive formulations and their role in gastroretention is also being discussed in this review. This review gives a full summary on gastroretentive drug delivery systems.

Ashwagandha, Tulsi, Mulethi, Awala, Shatavari, Gokharu, Arjun, Giloy, Safed musli, Kalimirchi, Haldi, Jaiphal can be used as an active ingredients and aqueous extract of Stevia rebaudiana as natural sweetener with nutraceutical in health dinks. The product can be developed by treating concentrates of each crude drug with purified water. TLC profile, HPTLC method development and validation can be carried out using Gallic acid as a standard. A new simple, sensitive, selective, precise and robust HPTLC method for analysis of Gallic acid in health drink can be developed. Precoated silica health drink aluminium plate 60F-254 (20 × 10 cm) with 200 µm thickness can be used as stationary phase while toluene: ethyl acetate: formic acid: ethanol (6: 4: 0.3: 0.4) system can be developed as a mobile phase. Spectrum analysis showed the same Rf values and spectrum pattern of standard and sample. The method can be validated by using accuracy, precision, linearity, robustness, ruggedness and recovery as applicable parameters. The developed method can be quite good and most sensitive for the present products. The unpleasant and bitter taste of the product can be masked by different concentrations of aqueous extract of Stevia. Sweetness potency can be determined by taste evaluation method. 1% Stevia extract may be sufficient to produce most palatable and acceptable sweet preparation.