Formulation development and optimization studies of mouth dissolving tablets of tizanidine HCl.

The purpose of this research was the development and optimization of mouth dissolving tablets (MDT) of Tizanidine hydrochloride using superdisintegrant. MDTs of Tizanidine (4mg) were manufactured by direct compression method. Formulations comprised of Tizanidine and excipients including croscarmellose sodium, Avicel PH 102, aspartame, orange flavor and magnesium stearate. Blends of powder were assessed for flow characterization and then compressed by direct compression. During post compression stage, a detail evaluation of tablets with respect to weight variation, hardness, thickness, disintegration time, wetting time, friability, drug content analysis, content uniformity, palatability and dissolution studies was carried out. All the formulations complied with the pharmacopeial requirements of weight, disintegration time and assay. Amongst the trial formulations F4 with concentration of croscarmellose sodium i.e. 5% was proved as best optimized due to satisfactory quality attributes such as least disintegration time and sufficient hardness. Hence, it was concluded that manufacturing of mouth dissolving tablets by addition of superdisintegrant is beneficial for treating patients with dysphagia.

Formulation development and in vitro evaluation of fast dispersible, taste masked aceclofenac compacted pellets.

The objective of study was to develop Aceclofenac fast dispersible compacted pellets with improved taste and fast drug release. Pellets were prepared by extrusion spheronization technique followed by direct compression to make compacted pellets. Formulations were comprised of sucrose, mannitol, ac-di-sol, aspartame, pine apple flavor and magnesium stearate. A mixture of distilled water and isopropyl alcohol (1:1) was used for wet massing. The effect of ac-di-sol on the drug release pattern was examined and dissolution profile comparison was established. All formulations followed First order and Weibull models and f2 values indicated dissimilarity with the marketed immediate release product. Taste of compacted pellets was evaluated by a panel of 12 human volunteers. Formulation P5 was found to be an optimized formulation due to satisfactory quality attributes.

Development & validation of reversed phase HPLC method for quantification of water insoluble API.

In the present work a specific, accurate, precise, and reproducible UV-HPLC method was developed and validated for the analysis of Aceclofenac. This method involved elution of Aceclofenac in a mobile phase which is composed of buffer pH 6.8 (i.e. using 0.01N KH2PO4) and HPLC grade Acetonitrile (60:40). Separation of the analyte was achieved using HPLC isocratic pump attached to the UV-VIS detectorC18, guard column and C18 column. The injection volume was 20µL, detected at 274 nm; flow rate: 1mL/min. Standard calibration curve was measured and found linear from 0.1 to 40µg/ml. The validation parameters were measured according to FDA guidelines and successful results were obtained. The presented analytical method could be employed for pharmacokinetic studies.

Intermediate release formulations of diclofenac potassium tablets for IVIVC.

In recent days response surface methodology (RSM) has widely been applied for development and optimization of cost effective formulations with required quality. Study comprised of three steps including micromeritic comparison of different powder blends of placebo and diclofenac potassium (DP), formulation designing with CCRD (Design Expert, version 7.0.0), and stability testing of selected formulations by using R Gui. Ten formulations (F11-F20) were developed using microcrystalline cellulose (Avicel PH-102) (X1) (13-72%), methocel K15M (X2) (6.59-23.4%) and magnesium stearate (X3) (1.32-4.68%), while responses were % friability and % drug release. Blending rate constant was determined at 3, 6, 9 and 12 minutes. The results of physicochemical parameters were found within acceptable limits. After in vitro testing at pH 1.2, pH 4.5 and pH 6.8, mechanism of drug release, kinetic analysis and statistical evaluation were carried out by model - independent, model-dependent and one-way ANOVA methods. Most formulations followed zero order kinetics at higher pH. Fickian release (0.326 ≤ n ≤0.449) was observed with ß greater than 0.5 and less than 1. ANOVA indicated no significant variation within and between formulations as p-values were found to be > 0.05.

Evaluation of Phytochemical Contents, Antimicrobial, and antioxidant Potential of Haloxylon Griffithii Collected From Northern Region of Balochistan, Pakistan.

Background: The therapeutic potential of Haloxylon griffithii found in northern region of Balochistan, so far has been neglected. Purpose: The current study was aimed to assess the phytochemicals and pharmacological potential of fractions isolated from H griffithii. Research Design: During phytochemicals analysis of H griffithii using GC/MS showed various bioactive compounds like alkaloids, flavonoids, terpenoids, tannins, saponins, and carboxylic acids. In vitro antioxidant activity of H griffithii was determined by 2, 2'- diphenyl-1-picrylhydrazyl (DPPH) assay. Disc diffusion method was used to evaluate the antimicrobial activity. Results: The quantitative analysis of ethyl acetate showed highest total flavonoid contents (1.19 ± .05) while ethanol with lowest value (.52 ± .01). The total phenolic contents in ethyle acetate was 1.50 ± .42, whereas ethanol showed lowest value (.77 ± .02). Ethanol exhibited excellent (88.68 ± 3.0) free radical scavenging potential measured by 1,1-diphenyl-2-picryl-hydrazyl radical scavenging assay. For antimicrobial activity, different bacterial and fungal strains like B subtilis, S aureus, E coli, S typhi, C albicans, and A. niger were selected. The essential oil showed maximum % inhibition diameter (9 mm) against B. Subtillus and (5 mm) against C albicans, respectively. The ethyl acetate presented % inhibition diameter (9 mm) against S aureus and (6 mm) against A niger. Anti-urease activity also showed positive response. Conclusions: The presence of high (%) bioactive compounds with great therapeutic potential suggest that H griffithii can be used as natural alternative of synthetic drugs without side effects.

Evaluation of medication errors in patients with kidney diseases in Quetta, Pakistan.

BACKGROUND: Medication errors represent a significant challenge in healthcare, as they can lead to enduring harm for patients and impose substantial financial burdens on the healthcare system. To effectively mitigate medication errors, it is imperative to gain a comprehensive understanding of their frequency and the contributing variables. Thus, the primary objective of this study was to evaluate the occurrence of medication errors among patients with kidney diseases in Quetta, Pakistan. METHODS: The objective of this study was to assess medication errors in patients diagnosed with kidney diseases in Quetta, Pakistan. The research was conducted at the Balochistan Institute of Nephro-Urology Quetta (BINUQ) Hospital, which serves as a tertiary care center specializing in the treatment of kidney diseases. A cross-sectional descriptive study design was employed over a period of six months. The study population consisted of patients admitted to the Nephro-urology wards at BINUQ Hospital during the specified duration. Data collection encompassed various methodologies, including checklist-guided observation, review of prescription order forms, documentation of drug administration, and comprehensive analysis of patient medical records. Descriptive and analytical analyses were conducted using SPSS version 23. Univariate analysis was employed to identify independent variables associated with medication errors, employing a significance level of p<0.01. The multivariate logistic regression analysis incorporated variables that exhibited a significant association with medication errors during the univariate analysis. Only those variables demonstrating a p-value of less than 0.05 at a 95% confidence level were considered significant predictors of medication administration errors within the final multivariate model. RESULTS: Among the 274 medication errors identified in the study, documentation errors accounted for 118 cases (12.06%), administration errors for 97 cases (9.91%), prescribing errors for 34 cases (3.47%), and dispensing errors for 25 cases (2.55%). Statistical analysis revealed significant associations (p<0.05) between forgetfulness and duty shift, and medication errors in the documentation process. Similarly, inattention was significantly associated (p<0.05) with both prescribing and dispensing errors. Furthermore, the number of medications received emerged as the most influential factor associated with medication errors. Patients receiving 4-6 medications exhibited an odds ratio of 9.08 (p<0.001) compared to patients receiving 1-3 medications, while patients receiving more than 6 medications had an odds ratio of 4.23 (p<0.001) in relation to patients receiving 1-3 medications. CONCLUSION: In conclusion, this study determined that documentation errors were the most prevalent medication errors observed in patients with kidney disease in Quetta, Pakistan. Forgetfulness and duty shift were associated with documentation errors, whereas inattention was linked to prescribing and dispensing errors. The significant risk factor for medication errors was found to be a high number of prescribed medications. Therefore, strategies aimed at reducing medication errors should prioritize enhancements in documentation practices, alleviating medication burden, and increasing awareness among healthcare providers.

Public awareness regarding the manufacturer provided information about medicine usage, safety, and adverse drug reactions in Balochistan, Pakistan.

Objectives: This study aimed to analyze the general public's awareness of medicine information, safety, and adverse drug reactions in Quetta, Pakistan. Methods: A cross-sectional descriptive study was conducted using random sampling from April 2020 to April 2021 in Quetta. Samples were collected from respondents who met the inclusion criteria and had visited community pharmacies. The analysis was done using SPSS version 23. Bivariate and multivariate analyses were performed to assess factors associated with good knowledge. Results: Multivariate analysis revealed that purchase on prescription was a determining factor of knowledge regarding knowledge of pharmaceutical products and their provided information, medicines usage and safety, and Medication ADRs. Patients who bought medicines on prescriptions were more likely to have better knowledge. Patients having education were more likely to have better knowledge. Conclusion: Public awareness about medicine information, safety, and the information provided by manufacturers is crucial to ensuring that patients have access to accurate information about their medications and can make informed decisions about their health. Healthcare providers and regulatory bodies must work together to improve access to information and promote safe medication practices.

Biochemical analysis and investigation on the prospective applications of alkaline protease from a Bacillus cereus strain.

Proteases have prospective financial and environment-friendly applications; hence attention is focused currently on the finding of new protease producing microorganism so as to meet the requirements of industry. A thermophilic bacterial strain producing extracellular protease activity was isolated from soil and identified as Bacillus cereus by analysis of 16S rRNA. Protease production by the microorganism was improved by studying the impact of the type of nitrogen and carbon source, fermentation period, growth temperature and initial pH of the culture medium in cultivation optimization experiments. The enzyme was purified to homogeneity in two step procedure involving Sephadex G-75 and Q-Sepharose chromatography. The molecular weight of purified enzyme was found to be 58 kDa by SDS-PAGE. Protease exhibited a pH and temperature optima of 7.5 and 60°, respectively. The enzyme was active in the pH range of 6.0-9.0 and stable up to 70°C. Histological analysis of protease treated goat and cow skin pelts showed complete removal of non leather forming structures such as hair shaft, hair follicles and glandular structures. The protease showed the stain removing property from blood stained cotton cloth and found to be compatible with six commercially available detergents. The protease could release peptides from natural proteins after digestion of coagulated egg albumin and blood clot.

Insulin deficiency among newly diagnosed type 2 diabetics.

BACKGROUND: Any patient above the age of 40 years, coming with the symptoms of diabetes is labelled as type 2 diabetic. If insulin levels are included in the protocol for initial investigations of diabetic patients, they can be differentiated as having insulin deficiency or insulin resistance. They can thus be treated accordingly. This study was conducted to see the prevalence of insulin resistance and insulin deficiency in newly diagnosed type 2 diabetics. METHODS: This study was conducted on 75 newly diagnosed diabetic subjects, and 75 control subjects for comparison. Fasting serum insulin was assayed by ELISA and HOMA-IR index was calculated. The diabetic subjects with fasting hyperglycaemia and serum insulin level below 20 microIU/ml and HOMA-IR index below 3.5 were grouped as insulin deficient (Group-A), and the diabetic subjects with fasting insulin level above 20 microIU/ml and HOMA-IR index above 3.5 were grouped as insulin resistant (Group-B). RESULTS: Twenty-eight percent subjects were found to have insulin level below 20 microIU/ml while 72% subjects had insulin resistance. When gender was taken into consideration, it was seen that 18.7% males had fasting insulin level of 6.98 +/- 0.737 microIU/ml and 9.3% females had fasting insulin level of 5.21 +/- 0.885 microIU/ml while 32% males and 40% females had insulin resistance. The mean age of male subjects with insulin resistance was significantly higher compared to the male subjects with insulin deficiency. Mean weight and body mass index of the male and female subjects having insulin resistance was significantly higher than their respective control groups and also higher than the subjects with insulin deficiency. Pearson coefficient of correlation was calculated for fasting serum insulin level with age and BMI. A significant positive correlation was observed between fasting serum insulin and age of females with insulin resistance. CONCLUSION: A considerable number of persons who develop diabetes after 40 years of age but are not insulin resistant. Twenty-eight percent subjects have relative insulin deficiency, and 72% subjects have insulin resistance.

Biosorptive Potential of Pseudomonas species RY12 Toward Zinc Heavy Metal in Agriculture Soil Irrigated with Contaminated Waste Water.

Industrial waste is mainly responsible for accumulating Zn (II) in the soil, which needs to be removed to avoid its bioaccumulation and hazardous effects on the environment. In a recent study, the potential of the RY12 strain was evaluated as a biosorbent of Zn (II) ions in an aqueous medium. Different microbiological techniques like biochemical, molecular characterization, and 16S rRNA gene sequencing were used for the identification of RY12. The impact of different parameters such as the initial zinc ion concentration, pH, temperature, and the removal of other metals such as manganese, lead, cobalt, silver, copper, mercury, and chromium was also evaluated on the reduction of Zn (II). Fourier Transform Infrared spectroscopy (FTIR) was also carried out to investigate the role of cellular surfaces in the sorption of Zn+2 ions. Both biochemical and phylogenetic analyses established that strain RY12 Pseudomonas sp. capable of reducing Zn+2 up to 89% at 28°C (pH = 6.5; initial Zn+2 concentration = 200 mg/L). The FTIR analysis revealed that the bacterial cell wall's amino, carboxyl, and phosphate groups were involved in the reaction with Zn (II). Our findings suggest that Pseudomonas sp. RY12 is a proficient bacterium for removing zinc from industrial waste and could be a valuable bioremediation agent.

Green Synthesis of Silver Nanoparticles (AgNPs), Structural Characterization, and their Antibacterial Potential.

Background: In the field of nanotechnology, the metallic nanoparticles are of remarkable interest because of their unique electronic, magnetic, chemical, and mechanical properties. Purpose: In the present work, silver nanoparticles (AgNPs) were synthesized using bio-reduction method. Research Design: Silver nitrate was used as metallic precursor and the extract of Moringa oleifera leaves with different concentrations was used as reducing as well capping agent. The extract exhibited strong potential in rapid reduction of silver ions for the synthesis of silver nanoparticles. The synthesized silver nanoparticles were characterized by UV-visible spectroscopy, X-ray diffraction (XRD), and scanning electron microscopy (SEM) techniques. Results: The absorption SPR peaks appeared in the range of 415 to 439 nm. SEM analysis exhibited that particles were spherical in shape with size distribution range from 10 nm to 25 nm. The synthesized silver nanoparticles were pure crystalline in nature as confirmed by the XRD spectra with average crystallite size 7 nm. In vitro antibacterial activity of the prepared silver nanoparticles colloidal samples as well the extract was studied using different concentrations of AgNPs (C1 = 100 µg/ml, C2 = 50 µg/ml, C3 = 25 µg/ml) by well diffusion method against Gram negative Escherichia coli. The antibacterial performance was assessed by measuring the zone of inhibition (ZOI). Conclusions: The results suggested that AgNPs prepared by green approach can be considered as an alternative antibacterial agent.

Factors and Predictors of Health Related Quality of Life of the General Population of Pakistan.

Background and Objective: The standards of living, improvement in public health, and medical care in Pakistan are increasing day by day, health-related quality of life (HRQoL) has been increasingly acknowledged in various patient's reported outcomes in Pakistan. However, a large-scale general population-based study on assessing HQRoL in Pakistan was not conducted. Therefore, this study aimed to evaluate HRQoL for the general Pakistani population. Material and Methods: A cross-sectional study with a population sample (n = 16,672) was selected from all Pakistan provinces using a stratified sampling approach. The EQ-5D-3L tool was used to measure the HRQoL of the general population of Pakistan. The descriptive and inferential statistics have been done by using SPSS version 20. Results: Overall, 121 health states were reported in this study. EQ-5D index and EQ-VAS scores were 0.74 ± 0.32 and 0.75 ± 0.25, respectively. The percentage of people responding to any problems increased with age. Males have better health as compared to females in all age groups. All demographics were significantly associated (P < 0.01) with the mean EQ5D index and VAS scores except residence (p > 0.05). The regression model reported that age was the best predictor of the EQ-5D index scores after adjusting for the covariates (beta = 0.19; p < 0.001). This study provides Pakistani population HRQoL data measured by the EQ-5D tool, based on a national representative sample. Conclusion: The current study concluded that Age, City, Gender, Education, Occupation, Residence, and House occupancy are significantly affecting HRQOL. The socioeconomically deprived groups and females have inferior health status than more advantaged. The trends detected in high-income nations were usually similar to Pakistan.

Isolation, Characterization of Zn Solubilizing Bacterium (Pseudomonas protegens RY2) and its Contribution in Growth of Chickpea (Cicer arietinum L) as Deciphered by Improved Growth Parameters and Zn Content.

Background: Zinc is an essential micronutrient required for optimum plant growth. Zinc-solubilizing bacteria convert applied inorganic zinc to available forms that could be used by plants. Research design: In present study, experiments were conducted to isolate, characterize, and evaluate Zn solubilization potential of different bacteria. Results: Among 10 isolated strains, Pseudomonas protegens (RY2, MF351762) was found to be the most promising strain having zinc-solubilizing potential on 4 different insoluble zinc sources. In quantitative assay, Zn solubilization by RY2 was significantly higher than other strains at different incubation time. P. protegens RY2 was selected (based on zinc solubilizing and plant growth promoting activities like P solubilization and ACC deaminase) for plant experiments. Meanwhile, available Zn release rate in soil was determined at day 10 of incubation. Chickpea seeds were inoculated with RY2 strain and ZnO is used as zinc source. Growth parameters and quantifying zinc content of shoot and root using atomic absorption spectrophotometer were determined. Enhanced shoot and root dry weights and lengths were observed in chickpea plants compared to control. Maximum increase of 44%, 67%, and 75% in T2 (Soil + RY2), T5 (Soil + ZnO + RY2), and T7 (Soil + manure + ZnO + RY2), respectively, was found in shoot length compared to control (T1). Conclusion: The study indicated that zinc-solubilizing RY2 strain possesses potential for enhanced Zn in soil so it would allow reduced inorganic Zn application.

Pre and post cloning characterization of a beta-1,4-endoglucanase from Bacillus sp.

Consistent with its precloning characterization from the cellulolytic Bacillus sp., beta-1,4-endoglucanase purified from the recombinant E. coli exhibited maximum activity at 60 degrees C and pH 7.0. It was highly specific for CMC hydrolysis, with stability up to 70 degrees C and over a pH range of 6.0-8.0. The K(m) and V(max) values for CMCase activity of the enzyme were 4.1 mg/ml and 25 micromole/ml min(-1), respectively. The purified enzyme was a monomer of 65 kDa, as determined by SDS-PAGE. The presence of sucrose and IPTG in fermentation media increased the endoglucanase activity of the recombinant enzyme to 5.2-folds as compared with that of the actual one.

Aceclofenac fast dispersible tablet formulations: Effect of different concentration levels of Avicel PH102 on the compactional, mechanical and drug release characteristics.

The objective of this study was based on the formulation development of fast dispersible Aceclofenac tablets (100 mg) and to evaluate the influence of pharmaceutical mixtures of directly compressible Avicel PH102 with Mannitol and Ac-di-sol on the compressional, mechanical characteristics and drug release properties. Fast dispersible Aceclofenac formulations were developed by central composite design (CCD). Among them the best possible formulation was selected on the basis of micromeritic properties, appropriate tablet weight and disintegration time for further study. Tablets were directly compressed using manual hydraulic press with a compressional force ranging from 7.2 to 77.2 MN/m2. Pre and post compression studies were performed and the compressed formulations (FA-FF) were assessed for different quality tests. The Heckel and Kawakita equations were applied for determination of compressional behavior of formulations. The quality attributes suggested that formulation (FB) containing avicel PH 102 (20%), mannitol (25%) and ac-di-sol (3%) as best optimized formulation showing better mechanical strength i.e. hardness 35.40 ± 6.93N, tensile strength 0.963 MN/m2, and friability 0.68%. Furthermore, compressional analysis of FB showed lowest PY value 59.520 MN/m2 and Pk value 1.040 MN/m2 indicating plasticity of the material. Formulation FB disintegrated rapidly within 21 seconds and released 99.92% drug after 45 min in phosphate buffer pH 6.8. Results of drug release kinetics showed that all formulations followed Weibull and First-order models in three different dissolution media. Avicel PH102 based formulation mixture exhibit excellent compactional strength with rapid disintegration and quick drug release.

Production, purification and characterization of beta-1,4-endoglucanase from a novel bacterial strain CTP-09 of a Bacillus sp.

Bacillus strain CTP-09 yielded maximum productivity (1120 IU/L.h) of extracellular endoglucanase (CMCase) on 0.5% cellobiose after 10 h fermentation at 55 degrees C. The purified enzyme is mono-meric in nature and exhibits stability up to 80 degrees C and over a pH range (6.0-9.0). Activation energy, enthalpy and entropy of catalysis, and inactivation indicated that this CMCase is highly thermos-table. Purified enzyme possessed high power of defibrillation of textile and was minutely inhibited by anionic detergent and oxidizing agent comparable with inhibition by commercial enzyme. This polypeptide could be exploited for mass production and application in local industries.