Preparation and Evaluation of a Self-Emulsifying Drug Delivery System for Improving the Solubility and Permeability of Ticagrelor.

Ticagrelor (TCG) is a BCS class IV antiplatelet drug used to prevent platelet aggregation in patients with acute coronary syndrome, having poor solubility and permeability. The goal of this study was to develop a self-nanoemulsifying drug delivery system (SNEDDS) of TCG to improve its solubility and permeability. The excipients were selected based on the maximum solubility of TCG and observed by UV spectrophotometer. Different combinations of oil, surfactant, and co-surfactant (1:1, 2:1, and 3:1) were used to prepare TCG-SNEDDS formulations, and pseudo-ternary phase diagrams were plotted. The nanoemulsion region was observed. Clove oil (10-20%), Tween-80 (45-70%), and PEG-400 (20-45%) were used as an oil, surfactant, and co-surfactant, respectively. The selected formulations (F1, F2, F3, F4, F5, and F6) were analyzed for ζ potential, polydispersity index (PDI), ζ size, self-emulsification test, cloud point determination, thermodynamic studies, entrapment efficiency, Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), in vitro dissolution, ex vivo permeation, and pharmacodynamic study. The TCG-SNEDDS formulations exhibited ζ potential from -9.92 to -6.23 mV, a ζ average of 11.85-260.4 nm, and good PDI. The in vitro drug release in phosphate buffer pH 6.8 from selected TCG-SNEDDS F4 was about 98.45%, and F6 was about 97.86%, displaying improved dissolution of TCG in 0.1 N HCl and phosphate buffer pH 6.8, in comparison to 28.05% of pure TCG suspension after 12 h. While the in vitro drug release in 0.1 N HCl from F4 was about 62.03%, F6 was about 73.57%, which is higher than 10.35% of the pure TCG suspension. In ex vivo permeability studies, F4 also exhibited an improved apparent permeability of 2.7 × 10-6versus 0.6708 × 10-6 cm2/s of pure drug suspension. The pharmacodynamic study in rabbits demonstrated enhanced antiplatelet activity from TCG-SNEDDS F4 compared to that from pure TCG suspension. These outcomes imply that the TCG-SNEDDS may serve as an effective means of enhancing TCG's antiplatelet activity by improving the solubility and permeability of TCG.

Formulation and characterization of orodispersible film containing diltiazem hydrochloride with taste masked effects.

Orodispersible film (ODF) is a better alternate to oral disintegrating tablets owing to its ease in application and subsequent patient compliance. This study investigates an improvement in physico-mechanical properties and palatability of Diltiazem Hydrochloride (DTZ) by formulating ODF employing solvent casting method. DTZ, used in the treatment of angina and hypertension, undergoes extensive presystemic metabolism and gives an incomplete bioavailability of 35-40%. DTZ also manifests a very bitter taste and after taste. DTZ was formulated into films using different polymer concentrations of Hydroxypropyl methylcellulose ethocel5 and Carboxymethyl cellulose and plasticizer levels of Propylene glycol and Glycerin to screen appropriate polymer-plasticizer combination. Optimized film disintegrated in 10.0±1.53 sec and appeared to be clear and smooth and almost 100% of the drug release was achieved within 4min from the ODF. Film revealed a good mechanical strength with folding endurance of >260, tensile strength of 1.36±0.11 N/mm2 and % elongation of 15.47±0.47%. FTIR and DSC showed compatibility between the drug and polymer. Film demonstrated a slightly sweet taste and after taste as well as an acceptability by the human volunteers. In conclusion DTZ was successfully formulated into film with improved physical properties and taste and could be beneficial to patients with cardiovascular disorders.

Synthesis and evaluation of chitosan based controlled release nanoparticles for the delivery of ticagrelor.

The aim of this contemporary work was to formulate a controlled release mucoadhesive nanoparticle formulation for enhancing the oral bioavailability of Ticagrelor (TG), a BCS class IV drug, having low oral bioavailability of about 36%. The nanoparticles can act as efficient carriers for hydrophobic drugs, due to having high surface area and hence can improve their aqueous solubility due to their hydrophilic nature. The nanoparticles (NPs) of TG were formulated using chitosan (CH) as polymer and sodium tripolyphosphate (TPP) as cross-linker, by ionic gelation technique with varying concentrations of polymer with respect to TG and TPP. Characterization of prepared nanoparticles was carried out to assess zeta potential, size, shape, entrapment efficiency (EE) and loading capacity (LC), using zeta sizer, surface morphology and chemical compatibility analysis. Drug release was observed using UV-Spectrophotometer. By increasing concentration of CH the desired size of particles (106.9 nm), zeta potential (22.6 mv) and poly dispersity index (0.364) was achieved. In vitro profiles showed a controlled and prolonged release of TG in both lower pH-1.2 and neutral pH-7.4 mediums, with effective protection of entrapped TG in simulated gastric conditions. X-ray diffraction patterns (XRD) showed the crystalline nature of formed NPs. Hence, this effort showed that hydrophobic drugs can be effectively encapsulated in nanoparticulate systems to enhance their solubility and stability, ultimately improving their bioavailability and effectiveness with better patient compliance by reducing dosing frequencies as well.

Perceived risk and perceptions of COVID-19 vaccine: A survey among general public in Pakistan.

BACKGROUND: The coronavirus disease has become a global pandemic, and it continues to wreak havoc on global health and the economy. The development of vaccines may offer a potential eradication of COVID-19. This study evaluated the general knowledge, attitude, and perception of COVID-19 vaccines in the Pakistani population. METHODS: A self-reporting e-survey and questionnaire-based survey from vaccination centers of different cities of Pakistan among 502 participants were conducted. The questionnaire comprised four sections inquiring demographics, vaccination status, and perception or attitude towards the vaccine. Univariate logistic regression was applied to predict the knowledge, attitude and behavior of participants. RESULTS: The mean age of participants was 50.8±20.3 years. 53% of the participants have both doses of vaccine administered. Pain on the site of injection (49.8%) was the most common symptom, followed by asthenia (43.0%), muscle pain (29.5%), and swelling (24.5%) on the site of vaccine administration. Females complain of more symptoms than males. More severe symptoms were reported after the first dose of vaccine administration; these symptoms subsided within a week for most participants. Overall, the respondents have a positive attitude towards the vaccine. 47.4% are sure about the vaccine's efficacy, 48.6% said getting vaccinated was their own decision, and 79.9% also recommended others to get vaccinated. CONCLUSION: The study concluded that the Pakistani population has a positive attitude but inadequate knowledge towards COVID-19 vaccines. Immediate awareness and vaccination education programs should be conducted by the authorities to complete the mass vaccination schedule.

Preparation and Characterization of pH-Independent Sustained-Release Tablets Containing Hot Melt Extruded Solid Dispersions of Clarithromycin : Tablets Containing Solid Dispersions of Clarithromycin.

The limited solubility of clarithromycin (CAM), coupled with low bioavailability and rapid elimination, are major shortcomings, needed to be addressed to achieve optimum therapeutic goals. Therefore, sustained-release (SR) tablets containing solid dispersion (SD) granules of CAM were prepared in this study. Initially, SD granules of CAM were prepared by hot melt extrusion (HME) technique using Kollidon VA64 as a hydrophilic carrier. The saturation solubility of SD showed almost 4.5-fold increase as compared to pure CAM in pH 6.8 medium. In vitro drug dissolution data indicated a substantial increase in the dissolution of SD as compared to that of pure CAM. The thermal stability of drug, carrier, and SD at elevated HME temperatures was evident from the results of thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Powder X-ray diffraction (PXRD) data and scanning electron microscope (SEM) images revealed a decrease in the crystallinity and the uniform dispersion of drug, respectively. Moreover, Fourier transformed infrared spectroscopy (FT-IR) data confirmed the formation of hydrogen bond between the carbonyl group of drug and the hydroxyl group of carrier. SD loaded sustained-release (SD-SR) matrix tablets were prepared with hydrophobic polymers (Eudragit RS100 and Eudragit RL100). The pH-independent swelling and permeability of both polymers were responsible for the sustained drug release from SD-SR tablets. Pharmacokinetic (PK) studies suggested a 3.4-fold increase in the relative bioavailability of SD-SR tablets as compared to that of pure CAM.

Solubility and dissolution rate enhancement of ibuprofen by cyclodextrin based carbonate nanosponges.

In the present study nanotechnology approach, i.e., a cyclodextrin (CD) based carbonate nanosponge was used to improve the solubility and dissolution of ibuprofen. Solvent and ultrasound assisted methods were used to prepare nanosponges using two CDs (ß-CD and 2-hydroxypropyl-ß-CD (2HP-ß-CD)) and a cross-linker (CL) diphenyl carbonate (DPC) in varying molar ratios. Nanosponges were investigated for their solubilizing efficiency and phase solubility studies. Structural analysis by Fourier transform infrared (FTIR) and powder X-ray diffraction (PXRD), thermo-analytical characterization by differential scanning calorimetry (DCS), morphology by scanning electron microscopy (SEM). In-vitro drug release followed by in-vivo analgesic and anti-inflammatory studies were performed. 2HP-ß-CD based nanosponges (molar ratio 0.01:0.04) prepared by ultrasound assisted method showed the highest solubilizing efficiency (i.e., 4.28 folds). Stability constant values showed that all complexes were stable. Inclusion complexes of drug was confirmed by PXRD and DSC. SEM images showed porous structures confirming the formation of cross-linked network. Particle size was in the range of 296.8±64 to 611.7±32nm. In-vitro release studies showed enhanced dissolution profile from nanosponge formulation (~94% from I11) as compared to the pure drug (~45% Ibuprofen) in 120min. Significant (p<0.05) extent of pain inhibition and anti-inflammatory activity was observed for nanosponge formulation when compared with the pure drug. CD based carbonate nanosponges with better solubility, enhanced release profile, improved analgesic and anti-inflammatory activity were successfully formulated for ibuprofen.

pH-Responsive Nanocomposite Based Hydrogels for the Controlled Delivery of Ticagrelor; In Vitro and In Vivo Approaches.

BACKGROUND: Ticagrelor (TG), an antiplatelet drug is employed to treat patients with acute coronary syndrome, but its inadequate oral bioavailability due to poor solubility and low permeability restricts its effectiveness. PURPOSE: This contemporary work was aimed to design a novel pH-sensitive nanocomposite hydrogel (NCH) formulation incorporating thiolated chitosan (TCH) based nanoparticles (NPs) of Ticagrelor (TG), to enhance its oral bioavailability for effectively inhibiting platelet aggregation. METHODS: NCHs were prepared by free radical polymerization technique, using variable concentrations of chitosan (CH) as biodegradable polymer, acrylic acid (AA) as a monomer, N,N-methylene bisacrylamide (MBAA) as cross-linker, and potassium persulphate (KPS) as initiator. RESULTS: The optimum hydrogel formulation was selected for fabricating NCHs, considering porosity, sol-gel fraction, swelling studies, drug loading capacity, and TG's in vitro release as determining factors. Outcomes of the studies have shown that the extent of hydrogel swelling and drug release was comparatively greater at higher pH (7.4). Moreover, an amplifying trend was observed for drug loading and hydrogel swelling by increasing AA content, while it declined by increasing MBAA. The NCHs were evaluated by various physicochemical techniques and the selected formulation was subjected to in vivo bioavailability studies, confirming enhancement of bioavailability as indicated by prolonged half-life and multifold increase in area under the curve (AUC) as compared to pure TG. CONCLUSION: The results suggest that NCHs demonstrated a pH-responsive, controlled behavior along with enhanced bioavailability. Thus NCHs can be effectively utilized as efficient delivery systems for oral delivery of TG to reduce the risk of myocardial infarction.

Antibiotic Prescribing Practices and Errors among Hospitalized Pediatric Patients Suffering from Acute Respiratory Tract Infections: A Multicenter, Cross-Sectional Study in Pakistan.

Background and objective: The noncompliance of treatment guidelines by healthcare professionals, along with physiological variations, makes the pediatric population more prone to antibiotic prescribing errors. The present study aims to evaluate the prescribing practices and errors of the most frequently prescribed antibiotics among pediatric patients suffering from acute respiratory tract infections who had different lengths of stay (LOS) in public hospitals. Methods: A retrospective, cross-sectional study was conducted in five tertiary-care public hospitals of Lahore, Pakistan, between 1 January 2017 and 30 June 2017. The study population consisted of pediatric inpatients aged 0 to 9 years. Results: Among the 11,892 pediatric inpatients, 82.8% were suffering from lower acute respiratory tract infections and had long LOS (53.1%) in hospital. Penicillins (52.4%), cephalosporins (16.8%), and macrolides (8.9%) were the most frequently prescribed antibiotics. Overall, 40.8% of the cases had antibiotic prescribing errors related to wrong dose (19.9%), wrong frequency (18.9%), and duplicate therapy (18.1%). Most of these errors were found in the records of patients who had long LOS in hospital (53.1%). Logistic regression analysis revealed that the odds of prescribing errors were lower in female patients (OR = 0.6, 95% CI = 0.1⁻0.9, p-value = 0.012). Patients who were prescribed with ≥3 antibiotics per prescription (OR = 1.724, 95% CI = 1.1⁻2.1, p-value = 0.020), had long LOS (OR = 12.5, 95% CI = 10.1⁻17.6, p-value < 0.001), and were suffering from upper respiratory tract infections (URTI) (OR = 2.8, 95% CI = 1.7⁻3.9, p-value < 0.001) were more likely to experience prescribing errors. Conclusion: Antibiotics were commonly prescribed to patients who had long LOS. Prescribing errors (wrong dose, wrong frequency, and duplicate therapy) were commonly found in cases of lower respiratory tract infections (LRTIs), especially among those who had prolonged stay in hospital.

Capacity and willingness to use information technology for managing chronic diseases among patients: A cross-sectional study in Lahore, Pakistan.

BACKGROUND AND OBJECTIVES: The information technology is a pivotal source of communication between patients and healthcare providers for managing chronic diseases. The objective of this study is to assess the capacity and willingness of patients to use information technology for managing chronic diseases. METHODS: A descriptive, cross-sectional study design was employed. Study was conducted in six tertiary care hospitals of Lahore, Pakistan. The study population consisted of patients aged ≥18 years and diagnosed with a minimum of one chronic non-communicable disease. A structured questionnaire was administered to the study participants for data collection. SPSS was used for data analysis. RESULTS: Among the 400 respondents, hypertension (39.5%) was the leading chronic condition followed by diabetes (27.5%). Majority of the patients owned a cell phone (90.7%) and had internet access (66.2%). Almost half of the respondents (51.0%) were willing to use text messages; whereas 78.5% and 75.7% of the respondents were reluctant to use video conference and e-mail as a source of communication with healthcare providers. Reason for unwillingness to use e-mail was the patients' desire to be directly examined by the doctor; whereas unfamiliarity with the use of text message and video conference was the major reason for not using these technologies. Logistic regression analysis revealed that interest in using e-mail to interact with specialist was more among those participants who had good self-reported health (OR = 2.579, 95%CI = 1.276-5.212, p = .008), access to internet (OR = 5.416, 95%CI = 2.777-10.564, p < .001), and those who owned a cell phone (OR = 12.944, 95%CI = 1.751-95.704, p = .012). Interest in using text messages to interact with specialist was more among participants with middle-income group (OR = 2.303, 95%CI = 1.389-3.818, p < .001), residency in close proximity to healthcare professional (OR = 3.529, 95%CI = 2.333-5.339, p < .001), access to internet (OR = 3.253, 95%CI = 2.102-5.033, p < .001) and among those who owned a cell phone (OR = 46.709, 95%CI = 6.335-344.377, p < .001). Interest in using video conference to interact with specialist was more among those participants who had access to internet (OR = 5.840, 95%CI = 2.825-12.069, p < .001) and among those who owned a cell phone (OR = 11.177, 95%CI = 1.510-82.725, p = .018). CONCLUSION: This study concluded that nearly half of the respondents were willing to use text messages; whereas, majority was reluctant in using video conference and e-mail as a source of communication with healthcare providers. Most of the respondents who were located farther from the health care provider were willing to use video conferencing in case it could save more than 60 minutes of their time.

In vitro to in vivo profiling: an easy idea for biowaiver study.

The aim of this article was to assess and apply the in vitro to in vivo profiling (IVIVP), a new biowaiver approach, in designing a product with specific release pattern. The IVIVP was established by plotting the observed and predicted plasma drug concentrations. For IVIVP, convolution approach was employed to estimate plasma drug concentrations from in vitro dissolution profiles. The IVIVP for T1S exhibited a good correlation coefficient (R2 = 0.963) followed by the T2 (R2 = 0.682), T3 (R2 = 0.665), T1 (R2 = 0.616), and Mepresso (R2 = 0.345). Establishing an IVIVP, based on the convolution approach, can be more useful and practicable in the biowaiver studies, rather than present not useful practice of IVIVC estimated via deconvolution approach. This paper also elaborates that there is good correlation between the in vitro and in vivo profiles of the developed metoprolol tartrate formulations, particularly for T1S.