ISSN: 2645-3258

Vol. 4 No. 1 (2021)

Original Research article


Effect of combination polymers of natural and semi synthetic origin on the drug release of Flavoxate. HCl

Raghavendra Kumar Gunda, Prasada Rao Manchineni, Rajini Sudireddy

International Pharmacy Acta, Vol. 4 No. 1 (2021), 2 June 2021 , Page 4e1:1-7
https://doi.org/10.22037/ipa.v4i1.34178

The objective of current work is to study the effect of combination of macromolecules (polymers) of natural (Lannea coromandelica gum) and semi synthetic (HPMCK100M) origin on the drug release of Flavoxate.HCl from the Gastro retentive floating formulation.  Flavoxate.HCl, an antispasmodic agent. Mainly used for treating urinary incontinence, urgency of urination. Floating tablets of Flavoxate.HCl were prepared using variable composition of HPMCK100M, Lannea coromandelica gum (LCG) with effervescent mixtures by direct compression technique. 9 formulations were made and evaluated for quality control parameters. From the obtained results clears that all formulations passes the compendial limits.  Data obtained from the dissolution study fitted well to kinetic modeling, kinetic parameters were determined. GRFX5 composed of 40 mg of HPMCK100M & 40 mg of LCG, is the best formulation showing similarity f2=84.66, f1= 4.29 with the marketed product (URISPAS). Formulation GRFX5 follow first order, whereas release mechanism found to be nonfickian type (n= 0.77).

Survey of Heavy Metals Residue (Ni and Cr) in raw Tarom rice and evaluation of cooking methods effectson the concentrations of thesemetals

Nafiseh Nasri Nasrabadi, Mohammad Shokrzadeh, Seyyed Nastouh Jalal Sadat, Maryam Alizadeh Chepy

International Pharmacy Acta, Vol. 4 No. 1 (2021), 2 June 2021 , Page 4e2:1-8
https://doi.org/10.22037/ipa.v4i1.25278

Introduction:
Consumption of food contaminated by heavy metals, especially nickel and chromium, cause adverse effects on human health, including impairment of renal function, met - hemoglobinemia, cirrhosis, and many other intoxication consequences. Since rice is one of the main meals of Iranian people, this project was conducted to determine the amount of contamination of nickel and chromium in rice , and to find how the cooking process may be effective on these elements. 
Materials and Methods:
Five samples were collected randomly from five geographic regions of Qaemshahr (i.e., North, South, East, West, and Center). Residues of nickel and chromium in raw and cooked rice were determined by the flame atomic absorption spectrophotometer (FAAS). Statistical analyses were done by SPSS V.18 software, and the
mean values of groups were comprised by ANOVA software.
Results:
The average values of nickel / chromium were 0.174 ±0.01 for raw rice and 0.036±000 for the rinsing water of cooked rice. The amount of these elements in the cooked rice by the “Virgo” cooking method was 0.12 ±0.0311 and for the “kateh” method (ordinary cooking of rice) was 0.142±0.035, respectively.
Conclusion:
The results indicated that the cooking processes of Virgo and Kateh methods had positive impacts on reducing the amount of nickel / chromium compared to the raw rice.

Design, synthesis and biological evaluation of new 2,5-diaryl-1,3,4-oxadiazole derivatives as selective cyclooxygenase-2 inhibitors

Teymour Vahedpour, Maryam Nazari, Elham Rezaee, Sayyed Abbas Tabatabai

International Pharmacy Acta, Vol. 4 No. 1 (2021), 2 June 2021 , Page 4e3:1-6
https://doi.org/10.22037/ipa.v4i1.34360

Introduction:


Non- steroidal anti - inflammatory drugs (NSAIDs) are common prescribed medications worldwide for the treatment of inflammatory conditions and pain. However, adverse effects of NSAIDs in long term use have led to investigation of selective cyclooxygenase - 2 (COX-2) inhibitors with reduced adverse reactions, including
gastrointestinal and cardiovascular side effects and nephrotoxicity.

Methods and Results:


In this study, a series of 2,5-diaryl-1,3,4-oxadiazole derivatives as novel selective inhibitors of COX-2 were rationally designed, synthesized, and biologically evaluated. The structures of compounds were confirmed with LC-Mass, IR, and 1H NMR spectra. Based on our results, most of the compounds had proper inhibitory activity against COX-2 similar to celecoxib, and exhibited selectivity towards COX-2 than COX-1. In this series, compound 5f, with nitro group in the R position, revealed the highest inhibitory activity and selectivity (IC50 = 19.6 µM, SI = 108.88) against COX-2. The docking study of compound 5a showed that this structure had appropriate affinity to the active site of the enzyme forming multiple hydrogen bonds.


Conclusions:


In summary, these structures will be a valuable lead scaffold to develop new potent and selective COX-2 inhibitors. 

The Effect of pH dependent and pH independent polymers on the drug release of anti-ischemic agent

Raghavendra Kumar Gunda, Prasad Rao Manchineni, K. Anil Kumar, D. Dhachinamoorthi, GSN Koteswara Rao

International Pharmacy Acta, Vol. 4 No. 1 (2021), 2 June 2021 , Page 4e4:1-6
https://doi.org/10.22037/ipa.v4i1.34400

The objective of current study is to study the effects of combination of pH independent (HPMCK100M) and dependent (partially neutralized; Eudragit L 100-55) polymers on the drug release of Ranolazine form extended release tablet formulation. Ranolazine, an anti-ischemic or anginal agent. Mainly used for treating exercise induced; variant and stable chronic angina pectoris along with myocardial infarction. Anti-ischemic effect exhibited by Ranolazine is independent of haemodynamic effects, due to this benefit; it was useful for treating patients, who were not responded to other anti-anginals. Extended release tablets of Ranolazine were prepared using various proportions of  Eudragit L 100-55,HPMCK100M in by direct compression technique. 9 formulations were developed and characterized for pharmacopoeial limits.  Data obtained from the dissolution study fitted well to kinetic modeling, kinetic parameters were determined. EHR5 containing 31.25 mg of Eudragit L 100-55& 31.25 mg of HPMCK100M, is the best formulation showing similarity f2=85.77, f1= 2.31 with the marketed product (RANOLAZ). Formulation EHR5 follow zero order, whereas release mechanism found to be nonfickian type (n= 0.653).

Prognostic Factors in Metformin Intoxication; A Case Control Study

Lida Shojaei Arani , Shahin Shadnia, Hoorvash Faraji Dana, Kiumars Bahmani, Nasim Zamani , Hossein Hassanian-Moghaddam, Mitra Rahimi, Nami Mohammadian Khonsari, Peyman Erfan Talab Evini

International Pharmacy Acta, Vol. 4 No. 1 (2021), 2 June 2021 , Page 4e5:1-4
https://doi.org/10.22037/ipa.v4i1.34565

Background: Metformin is one of the most orally used antidiabetic agents. Intentional and unintentional overdose of metformin can be associated with life threatening condition. In this study we evaluate prognostic factors for metformin intoxication.


Methods: This case-control study was performed on patients referred to Loghman Hakim toxicology emergency department due to metformin intoxication. The patient’s information and lab data were subsequently extracted from their medical file and data processing and analysis performed.


Results: There was a significant difference between two groups in multiple items, patients in died group had higher age, blood sugar, BUN, Cr, PT, INR, WBC, on the other hand this group had lower blood pressure, O2 saturation, pH, HCO3 and PTT. Receiver operating characteristic curve showed that five items including: Bp, O2sat, pH, HCO3 and Cr had ability to predict the risk of mortality in patients with metformin poisoning. Univariate as well as multivariate analysis showed, factors including: BP<95 (P=0.0184), O2sat<93 (P=0.0094), pH<6.94 (P0.0032), HCO3<17.25 (P=0.0302), and Cr>1.15 (P=0.0216) were related to patient’s mortality.


Discussion and conclusion: Our study showed that mentioned clinical and laboratory findings may have an important role in determining the prognosis of patients with metformin poisoning. Extracorporeal treatments may be considered sooner in those who have poorer prognostic factors since admission.

Preparation and Optimization of Vancomycin hydrochloride Encapsulated Multivesicular Liposomes for Sustained Locoregional Delivery

Melody Vatankhah, Arash Mahboubi, Azadeh Haeri, Seyed Baubak Mostafavi Naeini, Zahra Abbasian, Simin Dadashzadeh

International Pharmacy Acta, Vol. 4 No. 1 (2021), 2 June 2021 , Page 4e6:1-12
https://doi.org/10.22037/ipa.v4i1.34461

Introduction:


Osteomyelitis is a destructive inflammatory condition of the bone that is usually caused by a wide range of microorganisms especially Staphylococcus aureus. Considering the downsides of systemic antibiotic therapies as well as conventional local drug delivery systems such as using polymethylmethacrylate, this study aimed to develop, characterize and optimize vancomycin hydrochloride loaded multivesicular liposomes (MVLs) as a proper therapeutic option for the treatment of osteomyelitis.


Methods and Results:


A 23 full factorial design technique was applied to determine the effects of three variables (lipid to drug ratio, triolein content and cholesterol to phospholipid ratio) on the encapsulation efficiency and release profile of vancomycin hydrochloride loaded MVLs to optimize the final formulation. Further characterization was performed on the optimized formula by evaluating the morphology, size and storage stability. The average drug encapsulation efficiency and the mean diameter of the optimized formulation was 54.7 ± 0.3% and 9.019 ± 0.26 µm, respectively with a span value of 0.188. Additionally, the spherical and multivesicular nature of MVLs was visible using optical microscopy (x400). The optimized formula showed an in vitro sustained release characteristic with proper stability and insignificant change in size, morphology and EE% for 30 days at 4°C.


Conclusion:


This study suggests that vancomycin hydrochloride loaded MVLs might have the potential to be used in the treatment of chronic osteomyelitis as a biocompatible drug carrier with a high antibiotic entrapment capacity as well as controlled drug release.

The Effect of The Number of Potential Drug-Drug Interactions and Prescribed Medications on Length of Stay and Mortality Rate of Patients in The Intensive Care Unit

Elham Pourheidar, Rezvan Hassanpour, Donya Moslemzadeh, Majid Mokhtari, Mehran Kouchek, Mir Mohammad Miri, Mehrdad Haghighi, Mohammad Sistanizad

International Pharmacy Acta, Vol. 4 No. 1 (2021), 2 June 2021 , Page 4e7:1-4
https://doi.org/10.22037/ipa.v4i1.34106

Introduction: The incidence rate of potential drug-drug interaction (PDDIs) in medical prescriptions was reported from 5.4% to 63% depending on the studied population, duration of the study, and different methods used to classify this. The importance of DDIs is in terms of their impact on clinical outcome. The main aim of this retrospective study was the evaluation of the impact of DDIs on ICU outcome i.e. ICU Length of stay (ICULS) and mortality.


Methods and Results: The prescribed medications of 262 patients older than 18 years with ICULS more than 48 hours admitted to the ICU during 8 months were evaluated for the risk of PDDIs. We detected a significantly increased ICULS (from 7.03 ± 5.49 days to 19.14 ± 17.64 days, p=0.035) and mortality rate (OR, 3.76; 95% CI 1.47-9.62; p=0.006) in patients with at least one D or X interaction compared to those without them. The frequency of these interactions was 73.6%. We also observed a significant association between the number of prescribed medications (r=0.79, p=0.001) and PDDIs (r=0.86, p=0.001) with increased ICULS.


Conclusion: According to the high prevalence of PDDI among ICU patients due to their large number of prescribed medications, long time of treatment, and complicated diseases, and its significant positive correlation with ICULS and mortality, it is recommended monitoring the medications of patients who received more than 5 drugs for interactions to increase the chance of prevention of significant PDDIs and decrease LOS, costs, and mortality.

Sedative-Hypnotic Effects of Different Extracts and Fractions of Capparis Spinosa L. in Mice

mona khoramjouy, maede manaee, shamim sahranavard, Mehrdad Faizi

International Pharmacy Acta, Vol. 4 No. 1 (2021), 2 June 2021 , Page 4e8:1-6
https://doi.org/10.22037/ipa.v4i1.34526

Introduction: Capparis spinosa L. (Caper) is an aromatic plant growing in dry regions around the Mediterranean area. C. spinosa is shown to have several compounds such as tannins, sterols, alkaloids, polyphenols and flavonoids. Previous studies showed that flavonoids have sedative and hypnotic effects. The aim of this study was evaluating the sedative-hypnotic effects of various extracts and fractions of C. spinosa in different doses.


Methods and Results: Maceration method was used for extraction of the aerial part of the plant. All experiments conducted on male NMRI mice (18-25g weight). For evaluation the hypnotic and sedative effects of plant, open field and pentobarbital induced sleep test were used. In this study, animals were treated with different doses of aqueous extract, methanolic extract, methanolic fraction and dichloromethane fraction (i.p.). In pentobarbital induced sleep test, the duration of lack of righting reflex was reported. In open field test, the locomotor activities of mice were calculated by measuring total distance moved in the open field arena. According to the results, the dichloromethane fraction decreased the total distance moved in the open field test (ED50 = 66.6 mg/kg) and also increased the sleep duration in pentobarbital induced sleep test (ED50 =18.7 mg/kg) compared with other extract and fractions groups.


Conclusion: In conclusion, the dichloromethane fraction of C. spinosa has hypnotic and sedative effects compared to the other extract and fraction groups. Further studies are necessary to find the active components responsible for the several effects of the dichloromethane fraction and the exact mechanism of action of these effects.

SARS-CoV-2 emerges as a new curse to the life of global population. The infectivity and spreading rate of the disease makes it a pandemic with no such specific drug discovered yet. Considering the high spreading rate of the disease, there is an urgent need of selective anti-SARS-CoV-2 agent.  SARS-CoV-2 main protease is an important target involved in transcription of the viral RNA, inhibition of which may lead to virucidal action. Repurposing strategy proves some antivirals to be effective against Mpro, but safety issues are of concern. To identify lead, computational approaches are the best to consider. The present study incorporates three standard anti-HIV agents Lopinavir, Ritonavir and Indinavir to undergo pharmacophore modeling. The initial modeling resulted in the selection of few test compounds considering the low RMSD as observed in Zinc database. Rest of the compounds was designed from the pharmacophoric features of the newly developed model. 20 compounds were subjected to molecular docking. The docking results showed that, compound 20 revealed the highest binding energy (-8.6 kcal/mol), which is even lesser than all the three standards. The other compounds 3, 4, 5, 11 and 19 also responded well to the docking study. These six compounds were further evaluated for their drug-likeness and ADME properties to raise the acceptance level of the lead(s). Further computational study includes the Molecular-Dynamic simulation of the compound 20, to ensure no or lesser variations throughout the simulation analysis. The above sequential computational study provides a hypothetical guideline to optimize the lead as effective anti-SARS-CoV-2 agent.

Effect of vancomycin as antibiotic lock technique in prevention of catheter associated infection in stem cell transplantation patients

Soodabeh Shahkarami, Mahshid Mehdizadeh, Soheil Roshanzamiri, Maria Tavakoli Ardakani

International Pharmacy Acta, Vol. 4 No. 1 (2021), 2 June 2021 , Page 4e10:1-8
https://doi.org/10.22037/ipa.v4i1.35723

Introduction: This trial assessed the efficacy of vancomycin lock solution in reducing catheter-related blood stream infections among bone marrow transplantation patients who were transplanted using tunneled catheters.


Methods and Results: patients randomly received either heparin only (control group) or a mixture of 5 mg/ml vancomycin and 2500 U/ml heparin (antibiotic group) as catheter lock solution. Results: The control group, CRBSIs rates per1000 catheter-days was significantly lower (0.1609 vs 6.214 events; p=0.0265, Hazard ratio 4.924 %95 CI of ratio1.238-31.20) and BSI (Blood Stream Infection) rates per 1000 catheter-days was significantly lower (0.2744vs 3.644events; p=0.0073, Hazard ratio 7.209 %95 CI of ratio (0.03205-0.808)). More over, The cumulative infection-free catheter survival was significantly higher (log rank statistic 4.924 p=0.0265) in the antibiotic group and cumulative infection-free survival was significantly higher (log rank statistic 7.209 p=0.0073) in the antibiotic group compared with the control group. There is no significant difference in catheter removal incidence (27.27% in the antibiotic group vs 15.38% in the control group; p=0.245) between the two group.


Conclusion: Vancomycin containing catheter lock solution is effective in reducing CRBSIs incidence and prolonging central vein catheter survival in Hematopoietic stem cell transplantation (HSCT) patients.