Cardioprotective effect of 2-methoxy phenol derivatives against oxidative stress-induced vascular complications: An integrated in vitro, in silico, and in vivo investigation.

BACKGROUND: Oxidative stress and inflammation play crucial roles in macro/microvascular complications. Phenolic compounds and their derivatives show promise as therapeutic agents for diseases like cancer, metabolic disorders, and cardiovascular diseases. With their antioxidant and anti-inflammatory properties, these compounds hold potential for mitigating vascular complications and improving overall health. METHODOLOGY: This study aimed to assess the therapeutic potential of five 2-methoxy phenol derivatives (T2, T5, T6, T7, and T8) as antioxidants, anti-inflammatory agents, and vasorelaxants using in vitro, in silico, and in vivo approaches. RESULTS: Among all, T2 exhibited substantial antioxidant potential against 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radicals with IC50 (27.97 µg/mL), nitric oxide (NO) radicals (IC50 = 34.36 µg/mL), hydroxyl (OH) radicals (IC50 = 34.83 µg/mL) and Iron chelation (IC50 = 24.32 µg/mL). Molecular docking analysis confirms that all derivatives, particularly T2, exhibit favorable binding energies with the target proteins, ACE (-7.7 Kcal/mol), ECE-1 (-7.9 Kcal/mol), and COX-1 (-7.8 Kcal/mol). All of the compounds demonstrated satisfactory physicochemical and pharmacokinetic characteristics, and showed minimal to no toxicity during in silico, in vitro, and in vivo assessments. In isolated aortic rings from Sprague Dawley rats, pre-contracted with high K+ (80 mM), T2 induced vasorelaxation in dose dependent manner and shifted calcium response curves to the right as compared to verapamil. T2 also showed substantial platelet aggregation inhibition in a dose dependent manner with IC50 21.29 µM. All derivatives except T7 exhibited significant conservation of endogenous antioxidants i.e. catalase (CAT), peroxidase (POD), superoxide dismutase (SOD) and reduced glutathione (GSH) and significantly suppressed serum levels of inflammatory markers i.e. nitric oxide (NO), peroxides (TBARS), interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2). CONCLUSION: The study concludes that T2 has significant antioxidant potential and vasorelaxant effects with adequate pharmacokinetics, making it a promising lead compound for further molecular investigation in cardiovascular disorders.

In vitro evaluation of transdermal patches of flurbiprofen with ethyl cellulose.

This study was aimed to determine effects of penetration enhancers and plasticizers on drug release from rationally designed formulations of flurbiprofen based transdermal drug delivery system. Matrix type transdermal patches were formulated with ethyl cellulose (EC) as a polymer by using plate casting method. The plasticizers such as propylene glycol (PG) and dibutyl phthalate (DBP), and enhancers such as Span 20, Tween 20, sodium lauryl sulfate (SLS), isopropyl myristate (IPM) and ethanol (EtOH) were formulated in different concentrations in the patches. Such different combinations of polymer with various enhancers and plasticizers in patches were evaluated for their effect on the physicochemical properties and drug release behavior of flurbiprofen. The drug release study was carried out by the paddle-over-disk method and permeation of drug was performed by Franz diffusion cell using rabbit skin. Patches having ethanol with ethyl cellulose showed more uniformity in the physical properties while the smoothness and clarity of patches containing sodium lauryl sulfate were not satisfactory. The drug release from patches followed Higuchi and Korsmeyer-Pappas model while maximum drug release was obtained by isopropyl myristate (903 microg). It was concluded that the patches having ethyl cellulose with isopropyl myristate and propylene glycol are more useful for transdermal patches of flurbiprofen.

Impact of prescriber's handwriting style and nurse's duty duration on the prevalence of transcription errors in public hospitals.

AIMS AND OBJECTIVES: To investigate the prevalence of transcription errors in a main public hospital in Pakistan and to test the impact of medication name and dose writing styles and the nurse duty duration on the occurrence of transcription errors. BACKGROUND: Medication errors occur frequently in public hospitals. Errors occurring at the transcription stage have not been sufficiently investigated. DESIGN: Medications transcripts and dispensed item labels were prospectively reviewed. In the second stage, nurses (n=25) transcribed medication charts in a double-blind randomised cross-over design administered at one, six and 10 hours after the commencement of their duty. METHODS. Inpatient (n=1000), discharge patient (n=1000) medication transcripts and labels of dispensed items for (n=1000) transcripts were reviewed. On medication charts, orthographically similar medications (n=20) were written in lowercase and Tall Man, decimal doses were written covered and uncovered, and metric doses were written with and without trailing zeros. RESULTS: Of the 6583 and 5329 medications transcribed from inpatient and discharge patient charts, error rates were 16·9 and 13·8%, respectively. Labels for 6734 dispensed items were reviewed, and error rate was 6·1%. Tall Man, covered decimal points and avoiding trailing zeros with decimal units significantly reduced transcription errors. CONCLUSION: Errors increased with increasing nurse duty duration. Highlighting orthographically similar medications and the use of proper decimal and metric units reduce errors. RELEVANCE TO CLINICAL PRACTICE: Transcription errors are highly prevalent in Pakistan public hospitals; therefore, elimination of transcription stage is encouraged.

Inequalities in health care and behaviour in patients with diabetes and concurrent hypertension in Lahore, Pakistan.

The global healthcare delivery system is largely inequitable and patients suffer inequalities in relation to their socioeconomic status (SES). In this study, we applied univariate measures to predict the SES in a sample of patients. We investigated the relationship between patient's SES, adherence to drug, dietary intake and health behaviour. We also investigated if inequalities exist in physician's choice on multisource oral solid hypoglycaemic and antihypertensive drugs in a sample of male type II diabetes mellitus patients with concurrent hypertension. Questionnaires were administered on patients (N = 500) with diabetes mellitus and concurrent hypertension to determine their SES, prescribed drugs, dietary regime and health behaviour in Lahore, Pakistan. Correlation was determined using chi-square test for category characteristics, Kruskall-Wallis or ANOVA for continuous data variables non-normal or normally distributed data, respectively. The patient's SES was indicated by univariate like income, occupation, and education. Patients with high SES were more adherent to drug, dietary intake and health behaviour (Χ2 = 13.16, p < 0.001; 34.71, p < 0.0001; 79.24, p < 0.0001, respectively). Patients with lower SES were prescribed cheaper hypoglycaemic and antihypertensive alternatives than their richer counterparts (p < 0.0001). Socioeconomic differentials exist within urban communities; these differentials have direct effects on healthcare delivery and patient health.

Suitability of Gelucire 50/13 for controlled release formulation of salbutamol sulphate.

Gelucire 50/13 (G50/13) was assessed to develop controlled release formulation of salbutamol sulphate (SBL) a highly water soluble drug by semisolid matrix filling capsule technique. Drug release profiles of SBL release by using G50/13 and its blends with other hydrophilic or hydrophobic materials were investigated. Lipid matrix formulations prepared with increasing amount of polymer showed a substantial decrease in release rate of the drug while increasing drug amount in fixed polymer concentration did not significantly affect the release profile. Polyethylene glycol 6000 caused an increased water uptake resulting in fast erosion of the matrix whereas cetostearyl alcohol and stearic acid caused retardation in drug release. These findings confirm that a considerable amount of Gelucire is required alone or in combination with hydrophobic substances in order to sustain the release profiles of water soluble drugs. More linear profile was obtained by using matrix comprising Gelucire/stearic acid blend in more than 85% that was comparable to standard, Ventolin SR tablet. The test formulation showed a significant decrease at pH 1.0 and the drug release rate increased at high stirring speed. Moreover, short term stability of controlled release test formulation indicated slight increase in dissolution rate at high temperature.

Electronic prescribing reduces prescribing error in public hospitals.

AIMS AND OBJECTIVES: To examine the incidence of prescribing errors in a main public hospital in Pakistan and to assess the impact of introducing electronic prescribing system on the reduction of their incidence. BACKGROUND: Medication errors are persistent in today's healthcare system. The impact of electronic prescribing on reducing errors has not been tested in developing world. DESIGN: Prospective review of medication and discharge medication charts before and after the introduction of an electronic inpatient record and prescribing system. METHODS: Inpatient records (n = 3300) and 1100 discharge medication sheets were reviewed for prescribing errors before and after the installation of electronic prescribing system in 11 wards. RESULTS: Medications (13,328 and 14,064) were prescribed for inpatients, among which 3008 and 1147 prescribing errors were identified, giving an overall error rate of 22·6% and 8·2% throughout paper-based and electronic prescribing, respectively. Medications (2480 and 2790) were prescribed for discharge patients, among which 418 and 123 errors were detected, giving an overall error rate of 16·9% and 4·4% during paper-based and electronic prescribing, respectively. CONCLUSION: Electronic prescribing has a significant effect on the reduction of prescribing errors. RELEVANCE TO CLINICAL PRACTICE: Prescribing errors are commonplace in Pakistan public hospitals. The study evaluated the impact of introducing electronic inpatient records and electronic prescribing in the reduction of prescribing errors in a public hospital in Pakistan.

Gastrointestinal transit monitoring and absorption of controlled-release pellets of diltiazem.

The gastrointestinal (GI) transit and absorption of a multiparticulate controlled-release diltiazem formulation were investigated with reference to an innovator preparation. Transit of controlled-release pellets in GI tract was monitored using two marker drugs, namely paracetamol and sulfasalazine. Both formulations had little intersubject variation in gastric emptying and small intestine transit time. In both formulations, about 51% to 64% of the drug was absorbed while pellets were in the small intestine and the remaining amount while in the colon. The results found in this study were comparable to the other workers who used gamma scintigraphy or indirect method. Therefore, the method used in this study is a reliable alternative for studying GI transit of pellets.

Eudragit NE40-drug mixed coating system for controlling drug release of core pellets.

This study was aimed at developing a controlled-release coating system around core pellets with aqueous dispersion, along with some water channeling agents. Core pellets of diltiazem were prepared using the extrusion-spheronization technique and subsequently coated with aqueous dispersion of Eudragit NE40 alone, or drug-polymer mixtures using bottom-spray fluidized bed coater. The lag time in drug release profiles increased as the coating levels of Eudragit NE40 were increased, whereas no lag time was observed in core pellets coated with drug-polymer mixtures. Mixed coating at the 7% level exhibited comparatively better release profiles and provided desirable release rates during the 12-hour testing interval. Diltiazem HCl release from mixed coating was fairly independent of pH and drug loading. Curing of coated pellets was found to be an essential step for stable drug release profiles. The selection of core size range had remarkable effect on drug release rate and was considerably reduced by using greater core size.