Design, development and in vitro-in vivo study of colon specific fast disintegrating tablet based on time dependent approach

Targeted delivery systems for treatment of Inflammatory bowel disease (IBD) are designed to increase local tissue concentrations of anti-inflammatory drugs from lower doses compared with systemic administration The objective of this study was to formulate and evaluate an oral system designed to achieve site specific and instant drug release in colon for effective treatment of IBD based on time dependent approach. The system consists of core tablet containing model drug diclofenac sodium, superdisintegrant sodium starch glycolate, and coated with pH independent polymer Eudragit RSPO to achieve different total percentage weight gain. Drug release studies were carried out using changing pH method. Placebo formulation containing barium sulphate in the tablet was administered to human volunteers for in vivo X-ray studies. In vitro studies revealed that tablet with 5 % coating level release the drug after 5 h lag time corresponding to the colonic region. Tablets with 5 % coating level could maintain their integrity in human volunteers for 5 h, approximating colon arrival time and release the drug instantaneously. Colon targeting and instant drug release for 5 % coating level was due to swellable hydrophilic polymer, which is responsible for a lag phase preceding the onset of release and the immediate release effect of superdisintegrant, It was observed that as coating level increases, lag time also increases. This is because of increased diffusion path length and tortuosity at higher coating levels. In vivo - in vitro study reveals thickness of coating of Eudragit RSPO play an important role in colon delivery and tablet with superdisintegrant and 5 % coating level achieved the desired performance of the colon targeting.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Gastroretentive drug delivery system of captopril and hydrochlorothiazide bilayer tablet: formulation, optimization and in vivo evaluation

The purpose of the present study was to develop and optimize floating-bioadhesive bilayer gastroretentive drug delivery system (GRDDS) exhibiting a unique combination of floatation and bioadhesion to prolong residence in the stomach using captopril (CP) and hydrochlorothiazide (HCTZ) as a model drug. Captopril being unstable in intestinal pH and HCTZ has specific absorption from duodenum and the first part of the jejunum and to a small extent in the stomach are suitable candidate for GRDDS. 32 factorial design was employed in formulating and optimizing the GRDDS for bilayer tablet of CP and HCTZ matrix tablet. The main effect and interaction terms were quantitatively evaluated using a mathematical model. The gastroretentive ability of the tablets was evaluated by X-radiographic studies in healthy human volunteer. The tablet releases CP and HCTZ for extended period up to 24 h in controlled manner. The predicted values agreed well with the experimental values and the results demonstrate the feasibility of the optimization methodology in the development of GRDDS. The tablet was buoyant for up to 16 h in human stomach. Development of once a day gastroretentive formulation of CP and HCTZ improves the patience compliance and bioavailability of drugs.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Formulation and in-vitro evaluation of repaglinide microspheres prepared by spray drying technique

Repaglinide is a potent second generation oral hypoglycaemic agent widely used in treatment of non insulin dependent diabetic mellitus. The objective of the present study was to develop sustained release microspheres of repaglinide using ethyl cellulose and PEG 6000 as a matrix forming polymer. Microspheres were prepared by taking various concentrations of ethyl cellulose and PEG 6000 by spray drying technique. Prepared microspheres were evaluated for process yield, drug entrapment, particle size, SEM, FTIR, DSC and in vitro drug release. Process yield and drug entrapment was 40-45 % and 90-95 %, respectively. Particle size ranged in 5-22 µm and SEM study showed spherical shape and rough surface of microspheres. FTIR study and DSC analysis revealed the stable nature and amorphous dispersion of drug in the polymer matrix. In vitro release studies indicate retardation of release upto 12 h which can control both fasting blood glucose level and postprandial blood glucose.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Gastroretentive drug delivery system of captopril and hydrochlorothiazide bilayer tablet: formulation, optimization and in vivo evaluation

The purpose of the present study was to develop and optimize floating-bioadhesive bilayer gastroretentive drug delivery system (GRDDS) exhibiting a unique combination of floatation and bioadhesion to prolong residence in the stomach using captopril (CP) and hydrochlorothiazide (HCTZ) as a model drug. Captopril being unstable in intestinal pH and HCTZ has specific absorption from duodenum and the first part of the jejunum and to a small extent in the stomach are suitable candidate for GRDDS. 32 factorial design was employed in formulating and optimizing the GRDDS for bilayer tablet of CP and HCTZ matrix tablet. The main effect and interaction terms were quantitatively evaluated using a mathematical model. The gastroretentive ability of the tablets was evaluated by X-radiographic studies in healthy human volunteer. The tablet releases CP and HCTZ for extended period up to 24 h in controlled manner. The predicted values agreed well with the experimental values and the results demonstrate the feasibility of the optimization methodology in the development of GRDDS. The tablet was buoyant for up to 16 h in human stomach. Development of once a day gastroretentive formulation of CP and HCTZ improves the patience compliance and bioavailability of drugs.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Ileo-cecal targeting mucoadhesive budesonide tablet

Crohn's disease occurs at any part of gastro-intestinal tract (GIT) but the most susceptible is the ileo-cecal region. For an effective treatment of this disease is essential the drug to be released at ileo-cecal region for an extended period of time. The present study is an attempt to design and develop an ileo-cecal targeting mucoadhesive drug delivery system that may be released specifically and slowly in ileo-cecal region without being released in the upper GIT for an extended period of time (12 h). Budesonide mucoadhesive tablets are coated with Eudragit S100, which is a polymer that specifically dissolves at and above pH 6.8. The in vitro drug release by changing pH method was done and in vivo study using X-ray radiography was carried out to ascertain the position of tablets in GIT after specific time intervals. The in vitro performance of the tablet with 10 % w/w coating level showed that the tablet did not disintegrate till 16 h with constant drug release. An in vivo study also reveals that the tablet lasted till 16 h in the ileo-cecal region.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Dissolution Improvement of Poorly Water Soluble Drug Valsartan and Improving Flow Properties of Solid Dispersion

The aim of the present investigation is to improve the dissolution of poorly water soluble drug valsartan by preparing solid dispersions and also to evaluate the effect of different inert carriers on flow properties of solid dispersion. Valsartan is a poorly soluble drug useful in the treatment of hypertension. Absorption window of valsartan is stomach and upper part of small intestine. One possible way to improve dissolution rate is solid dispersions of the drug. The solid dispersions were prepared by solvent evaporation method using HPMC E5 LV as water soluble carrier, as use of HPMC low viscosity polymers for solid dispersion preparations were reported in literature. But film formation took place during solid dispersion formulation and was creating difficulty in releasing the drug from formulation; and those solid dispersions, were not free flowing. Thus such preparations are not useful from the formulation development point of view. So to improve the flow properties some inert material were tried like microcrystalline cellulose (MCC) and lactose. The solid dispersions were evaluated for drug content, solubility and dissolution studies. In vitro drug release of solid dispersions was studied by USP type II paddle dissolution apparatus. For the solid dispersion the solubility and dissolution of the drug increased with the increase in the carrier concentration. Probable mechanisms of improved solubility and dissolution were characterized by Differential Scanning Calorimetry (DSC), Powder X-ray Diffractometry (Powder XRD) and Scanning Electron Microscopy (SEM) of drug, physical mixture and solid dispersions. This study revealed that solid dispersions technique is promising and useful for valsartan to improve its solubility and dissolution and incorporation of inert carriers improved the flow property of solid dispersion.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Gastroretentive drug delivery system of captopril and hydrochlorothiazide bilayer tablet: formulation, optimization and in vivo evaluation

The purpose of the present study was to develop and optimize floating-bioadhesive bilayer gastroretentive drug delivery system (GRDDS) exhibiting a unique combination of floatation and bioadhesion to prolong residence in the stomach using captopril (CP) and hydrochlorothiazide (HCTZ) as a model drug. Captopril being unstable in intestinal pH and HCTZ has specific absorption from duodenum and the first part of the jejunum and to a small extent in the stomach are suitable candidate for GRDDS. 32 factorial design was employed in formulating and optimizing the GRDDS for bilayer tablet of CP and HCTZ matrix tablet. The main effect and interaction terms were quantitatively evaluated using a mathematical model. The gastroretentive ability of the tablets was evaluated by X-radiographic studies in healthy human volunteer. The tablet releases CP and HCTZ for extended period up to 24 h in controlled manner. The predicted values agreed well with the experimental values and the results demonstrate the feasibility of the optimization methodology in the development of GRDDS. The tablet was buoyant for up to 16 h in human stomach. Development of once a day gastroretentive formulation of CP and HCTZ improves the patience compliance and bioavailability of drugs.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Application of Tablet in Tablet technique to design and characterize immediate and modified release tablets of Timolol maleate

Hypertension is one of the major causes of mortality in the world. The non-selective -β-blocker which includes Timolol maleate (TM) is usually used in hypertension, at a given dose of 10–40 mg. The present research aims to design a tablet-in-tablet (TIT) formulation as a single-unit dosage form to achieve modified and rapid drug release. Wet granulation was used to create the inner core modified release tablet utilising the release modifying agent's Sodium alginate (SA) and Hydroxypropyl methylcellulose (HPMC K4M). The impact of independent factors, SA and HPMC K4M, in different percentages of w/w, which affect the in vitro drug release and swelling index, was investigated using a 32 complete factorial design. The TM outer instant-release shell, which was made using croscarmellose sodium and Microcrystalline cellulose (MCC) in three distinct sizes, was press-coated onto the optimised inner core tablet. The core and outer shell tablets are within acceptable ranges for several physicochemical properties. No indication of interactions between drugs, polymers, and excipients was found in the Fourier transform infrared (FTIR) and Differential scanning calorimetry (DSC) investigations. The inner core tablet's formulation F6 achieves a 96.38% in vitro drug release at 24 h and a swelling index of 52.7%. The TIT-2 was, however, considered as the final tablet-in-tablet formulation because contains fewer excipients and shorter disintegration time than TIT-3

A Modified Solvent Method for Preparation of Solid Dispersions: Preparation of solid dispersions

The first aim of the present investigation was to prepare solid dispersions to improve the dissolution properties of oxcarbazepine and quetiapine using PEG 6000 as a carrier with the help of two methods of preparations viz. spray drying and modified solvent method, and to compare the two methods. The second objective was to apply the modified solvent method for preparation of sustained releasesolid dispersions of domperidone with Eudragit RLPO as a carrier. The solid dispersions of oxcarbazepine and quetiapine were prepared using spray drying and a modified solvent evaporation method. The modified method was then used to prepare solid dispersion of domperidone. All the preparations were evaluated for solubility and dissolution. The characterization was done using FTIR, PXRD andDSC. The solubility and dissolution rates increased significantly for oxcarbazepine and quetiapine in the solid dispersion with PEG 6000. The release of domperidone was decreased in the solid dispersion with Eudragit RLPO. The solubility and dissolution rates of oxcarbazepine and quetiapine were increased significanly in the solid dispersions prepared by both spray drying and modified solvent method.There was no significant difference in the release profiles of solid dispersion prepared by the two methods. The modified solvent method was effectively used for preparing sustained release solid dispersion of domperidone

Outcome Prediction and Severity of Corona Virus Disease (COVID-19) on the Basis of Clinical and Laboratory Parameters

Background: Laboratory parameters play a key role in triaging, predicting disease course, severity and may determine prognosis COVID-19 patients. Material and methods: Aim and Objectives: To study the relation of clinical and laboratory parameters (total WBC count, neutrophil: lymphocyte ratio, serum ferritin, serum D-dimer, serum LDH, CRP, ESR) with severity and outcome of Corona Virus Disease (COVID-19) confirmed by real-time RT-PCR. Sample size: It was a time-bound study conducted over 3 months (1st April to 30th June, 2020). A total of 206 patients will be included in this study satisfying the inclusion criteria. Study design: This was a prospective, observational and non-interventional study conducted on patients with laboratory-confirmed COVID-19 admitted in a tertiary care teaching hospital. Statistical Analysis: Data will be analyzed for mean, percentage, standard deviation, and chi-square test for quantitative data by using appropriate statistical tests using INSTAT software version 8.0 (trial version) and p-value < 0.05 will be considered statistically significant. Results: Total of 206 patients of both genders were included in the present study. Total 141 (68.44%) patients were males and 65 (31.55%) patients were females (Chi Sq. 56.07; DF:1; p < 0.001). Among all the groups according to the severity of illness, ‘D’ group was the most common group (n = 99; 45.06%). Age > 60 years (17.48%), obesity (13.11%), hypertension (10.19%), COPD (5.83%), and diabetes mellitus (5.83%) were the most frequent risk factors or comorbidities associated with COVID-19 disease. Many patients had multiple risk factors in the present study. The majority (3/4th) of the patients were in C and D group (moderate) with co-morbidities and about 1/4th were in the severe group. Total 5 (2.43%) patients with COVID-19 patients succumbed to death with an overall case fatality rate of 2.43%. The case fatality rate was significantly higher among the patients with risk factors or comorbidities (p = 0.0124). Late presentation, associated comorbidity, advancing age, High level of ferritin, D-dimer, CRP, PaO2/FiO2 ratio less than 100 at the time of admission were associated with mortality. The terminal event in patients who have succumbed was bradycardia followed by cardiorespiratory arrest. The cause of death was ARDS with bilateral extensive pneumonia. Conclusions: Late presentation, associated comorbidity like diabetes mellitus, advancing age, High level of ferritin, D-dimer, CRP, PaO2/FiO2 ratio less than 100 at the time of admission were associated with mortality. The terminal event in patients who have succumbed was bradycardia followed by cardiorespiratory arrest. The cause of death was ARDS with bilateral extensive pneumonia