NEWER OPHTHALMIC IN SITU GEL OF MOXIFLOXACIN HYDROCHLORIDE: OPTIMIZATION USING BOX BEHNKEN STATISTICAL DESIGN

Objective: The present research work aims at describing the formulation and evaluation of the ocular delivery system of moxifloxacin hydrochloride (MH) based on the concept of ion sensitive in situ gelations. Methods: In situ gel was prepared by a hot method using 0.6% of gelrite, 0.25% hydroxypropylmethylcellulose (HPMC K4M) and 0.023% tamarind gum as bioadhesive polymers for sustained drug release. Optimization was done by Box Behnken Design with different concentration of gelrite (X1), HPMC K4M (X2) and tamarind gum (X3) as independent variables. In situ gel was optimized based on mucoadhesion index (Y1), Gel strength (Y2) and in vitro drug release (Y3). Influence of the quantitative variable on the dependent variable was predicted by a polynomial equation. Results: Infrared spectroscopy excluded any interaction between drug and excipients. The selected independent variables significantly influenced the responses and were able to sustain the drug release. The prepared gel with a pH of 6.8 to 7.4 exhibited non-newtonian flow with no ocular irritation. The formulation remained stable with no change in pH and viscosity after 30 d of stability study. Conclusion: Thus, moxifloxacin hydrochloride (MH) in situ gel is a viable alternative to a conventional delivery system with the properties of sustained drug release, prolonged ocular retention, and improved corneal penetration

Enhancement of Solubility of Artemisinin and Curcumin by Co-Solvency Approach for Application in Parenteral Drug Delivery System

The aim of present study was to enhance solubility of poorly soluble antimalarial drugs, Artemisinin and Curcumin by adopting  Co-solvency approach and to develop parenteral aqueous injectable solution. Solubility enhancement of both drugs was achieved using co-solvency approach. The parenteral injection was prepared by using a ternary co-solvent system which comprised of benzyl alcohol, PEG 400 and tween 80 (as surfactant). Solubility of Artemisinin and Curcumin was found to be higher in benzyl alcohol and PEG 400. Co-solvent system comprising of  benzyl alcohol, PEG 400 and tween 80 in volume fraction of 0.3, 0.9 and 0.2 respectively showed the minimum required solubility of Artemisinin (90 mg per ml) and Curcumin (180 mg per ml). The parenteral injectable formulation was characterized for pH, clarity, viscosity, osmolarity and sterility and the stated parameters were found in acceptable range.  In-vitro erythrocyte toxicity study showed that intravenous administration of optimized formulation will be safe. In-vitro antimalarial assay indicated that efficacy of artemisinin and curcumin parenteral formulation was greater than quinine and combination of Artemether and Lumefantrine. Stability study of the optimized batch showed no change in physical and chemical characteristics. Based on study, one can conclude that Artemisinin and Curcumin can be successfully formulated as parenteral injectable formulation by co-solvency approach for the effective treatment of malarial infectio

Čvrste disperzije silimarina: Karakterizacija i utjecaj načina priprave na oslobađanje

The influence of preparation methodology of silymarin solid dispersions using a hydrophilic polymer on the dissolution performance of silymarin was investigated. Silymarin solid dispersions were prepared using HPMC E 15LV by kneading, spray drying and co-precipitation methods and characterized by FTIR, DSC, XRPD and SEM. Dissolution profiles were compared by statistical and model independent methods. The FTIR and DSC studies revealed weak hydrogen bond formation between the drug and polymer, while XRPD and SEM confirmed the amorphous nature of the drug in co-precipitated solid dispersion. Enhanced dissolution compared to pure drug was found in the following order: co-precipitation > spray drying > kneading methodology (p sušenje sprejom > metoda gnječenja (p < 0.05). Iz svih pripravaka oslobađanje je bilo sporije, bez obzira na metodu priprave. Pripravci dobiveni metodom koprecipitacije bili su stabilni, a oslobađanje silimarina iz njih bilo je 2,5 bolje u odnosu na čisti lijek

IJPER Jan-Mar

The purpose of present study was to develop once a day sustained release enteric coated tablet of Fluoxetine HCl by direct compression method. Design was prepared for nine batch using fenugreek mucilage at 40%, 50% and 60% concentration ; HPMC at 10%, 15% and 20%; Compritol ATO 888 at 10%, 15% and 20% and ethyl cellulose at 2%, 3% and 4% concentration. Fenugreek mucilage was extracted from dried ripe seeds of Trigonella foenum-graecum (Fabaceae). Cellulose acetate phthalate was used as enteric coating agent. The tablets were characterized for weight variation, crushing strength, friability, drug content and in vitro drug release study. All the formulations were complied with standard specifications. The Drug excipients compatibility study was performed by DSC and IR Spectroscopy and no incompatibility was found. The results of in vitro dissolution studies indicated that formulations X2, X5 and X8 released 7.03%, 7.03%, 4.75% of Fluoxetine respectively at the end of 2 hour and 98.17%, 78.12%, 65.45% of Fluoxetine respectively at the end of 24 hour. Increased release rate was observed in polymer in the order HPMC K 100M &gt; ethyl cellulose &gt; Compritol ATO 888. Formulation X2 (50% fenugreek mucilage and 15% HPMC K 100M) could extend drug release up to 24 hour and it exhibited satisfactory drug release within first 2 hours and total release pattern was very close to marketed product. The 0 mechanism of drug release was found to be diffusion coupled with erosion. Optimized formulation was found to be stable when exposed to 40 C/ 75 % of relative humidity for 3 month

Right atrial intramural hematoma associated with aortic dissection

A 75-year-old male presented with shortness of breath and abdominal pain; he had undergone coronary artery bypass graft surgery three months ago and had a history of coronary artery disease, hypertension, and end-stage renal disease. Transthoracic echocardiogram showed a right atrial mass. A computed axial tomography scan showed an atrial mass and type A aortic dissection. The patient sustained cardiorespiratory arrest and died. An autopsy showed an 8 cm atrial intramural hematoma originating from a dissecting aneurysm. This is the first case of right atrial intramural hematoma associated with aortic dissection exhibiting high mortality. Early diagnosis using multiple imaging modalities including magnetic resonance imaging and timely surgical intervention may improve survival. Intramural hematomas should be considered in patients presenting with right-sided cardiac lesions

Amalgamation of nano and 3-D printing technology: Design, optimization, and assessment

Personalized medicine is the need of today's era, as one therapy does not fit all. The study aims to develop a novel patient-customized formulation using the integration of 3-D printing and Nanotechnology concepts. Valsartan (VLS) was chosen as a model drug for the study due to its poor bioavailability and dose-dependent toxicity. The Polycaprolactone (PCL)-VLS bionanoparticles (PCVBio) were formulated using a modified solvent evaporation method, inculcating the approach of Quality by Design (QbD). The amount of PCL and Polaxomer-188 (PLX) significantly influenced the PCVBio properties, which central composite design (CCD) ascertained. The results of DSC confirm the conversion of crystalline to amorphous structure. The zeta potential, PDI, and particle size ensure stability and nano size. The optimized PCVBio was further loaded into the multi-channel 3-D printed tablet (M3DPT). M3DPT was formulated by the fused deposition modeling method. The process parameters,% infill, and layer height significantly influenced the tablet's quality. The PCVbio M3DPT was able to release the VLS up to 12 h. The optimal formulation was found stable and effective. The new conjugated advanced formulation will improve the effectiveness, safety, and patient adherence. It unlocks the new research direction toward improving patients' lives

Dual-purpose Injectable Doxorubicin Conjugated Alginate Gel Containing Polycaprolactone Microparticles for Anti-Cancer and Anti-Inflammatory Therapy

In situ gel formulations have been widely reported as a carrier for sustained release delivery systems due to certain advantages such as targeted drug delivery, minimal invasiveness and potent therapeutic activity. Herein, in situ gel system for sustained release of doxorubicin and ibuprofen for anti-cancer and anti-inflammatory activity is reported. Doxorubicin-conjugated alginate (dox-alg) gel was prepared using EDC-NHS chemistry and loaded with ibuprofen encapsulated polycaprolactone (PCL) microparticles (dox-alg composite). PCL microparticles were prepared by a solvent evaporation method (size 50 - 100µm). The gel was characterized using SEM, FTIR, XRD and TGA analysis. Dox-alg composite gel showed good syringeability and gel formation properties. Burst release was observed for both drugs within 24 h followed by sustained release till day 21. Doxorubicin released from composite showed considerable cytotoxic effect. Cell uptake was confirmed by confocal microscopy using MDA-MB-231 cells. Anti-inflammatory activity of ibuprofen released from composite gel was compared with the free drug. An injection of dox-alg composite gel in the tissue would fill the void created after tumor removal surgery, prevent the resuscitation of remnant cancerous cells and reduce inflammation. Thus, the dox-alg composite gel could be a potential agent for the dual anti-cancer and anti-inflammatory therapy

Atovaquone smart lipid system: Design, statistical optimization, and in-vitro evaluation

The research was undertaken to design, develop and characterize the smart lipid system of an inadequate bioavailable Atovaquone (ATQ). The poor aqueous solubility and dissolution are the major constrain of inadequate bioavailability. The solubility study reveals that Labrasol-ALF (L-ALF), Tween 80, and Trancutol®P (TP) were screened as oil, surfactant, and co-surfactant, respectively. The pseudo ternary diagram was constructed to locate the appropriate amount of each ingredient, and a 1:3:1 ratio of l-ALF: Tween 80: TP was chosen. The effect of precipitation inhibitor was assessed using the parachute effect. Soluplus® (SP) was chosen as a precipitation inhibitor at 5%. Ishikawa diagram and qualitative risk assessment were performed to screen the critical material attributes (CMAs) and critical process parameters (CPPs). d-optimal mixture design was explored for the optimization of the formulation. The amount of oil, surfactant, and co-surfactant was screened as independent variables, whereas globule size, poly-dispersibility index (PDI), and solubility were designated dependent variables. The design batches were evaluated for the in-vitro dissolution rate, PDI, zeta potential, globule size, etc. The optimal region was located using an overlay plot. The optimized formulation has shown a 97.91% drug release within 1 h. The value of zeta potential (-27.43 mV) and PDI (0.468) indicates the stability of the formulation. The parachute effect had explored for the selection of precipitation inhibitors. SP was able to increase the solubility of ATQ and reduce the precipitation of the drug. The amount of l-ALF, Tween, 80and TP was significant for the formulation of SNEDDS. The formulation was novel, effective, patient-friendly, and industry oriented

Development and Validation of HPLC method for simultaneous estimation of Rifampicin and Ofloxacin using experimental design

A accurate, precise and robust isocratic HPLC method has been developed and validated for simultaneous determination of Rifampicin and Ofloxacin. The chromatographic separation was carried out on Kinetex C18, 100 A Phenomenex column with a mixture of 0.03M Potassium dihydrogen phosphate buffer pH 3.0: Acetonitrile (55:45) as mobile phase at 230 nm. The retention times were 2.91 and 4.87 min for Ofloxacin and Rifampicin, respectively. Calibration plots were linear over the concentration range 1–5 and 2–10 µg/ml for Rifampicin and Ofloxacin, respectively. The method was validated for linearity, sensitivity accuracy, precision, and robustness. Percent recoveries were found to be close to 100% with low variability. Fractional factorial design with four factors was chosen for robustness testing. The volume of acetonitrile and flow rate showed significant effect on retention factor of both the drugs and asymmetry factor of ofloxacin. The method may be adopted for routine analysis at industry

An unusual case of orbital involvement and pan-ocular inflammation in Acute Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease in which organs and cells undergo damage mediated by tissue-binding autoantibodies and immune complexes. At the onset, SLE may involve only one organ (additional manifestations may occur later) or multiple organs. The ocular manifestations are varied and involve the lids, cornea, sclera and or orbit. There may be associated secondary Sjogren's syndrome, conjunctival haemorrhages, retinal vascular disease with retinal haemorrhages and neuro-ophthalmic lesions. Pan-ophthalmic involvement is rare and sight threatening and requires urgent ophthalmic intervention. We hereby present an unusual case of pan-ophthalmic inflammation in case of acute systemic lupus