Biosynthesis of Polyhydroxyalkanoates (PHAs) by the Valorization of Biomass and Synthetic Waste.

Synthetic pollutants are a looming threat to the entire ecosystem, including wildlife, the environment, and human health. Polyhydroxyalkanoates (PHAs) are natural biodegradable microbial polymers with a promising potential to replace synthetic plastics. This research is focused on devising a sustainable approach to produce PHAs by a new microbial strain using untreated synthetic plastics and lignocellulosic biomass. For experiments, 47 soil samples and 18 effluent samples were collected from various areas of Punjab, Pakistan. The samples were primarily screened for PHA detection on agar medium containing Nile blue A stain. The PHA positive bacterial isolates showed prominent orange-yellow fluorescence on irradiation with UV light. They were further screened for PHA estimation by submerged fermentation in the culture broth. Bacterial isolate 16a produced maximum PHA and was identified by 16S rRNA sequencing. It was identified as Stenotrophomonas maltophilia HA-16 (MN240936), reported first time for PHA production. Basic fermentation parameters, such as incubation time, temperature, and pH were optimized for PHA production. Wood chips, cardboard cutouts, plastic bottle cutouts, shredded polystyrene cups, and plastic bags were optimized as alternative sustainable carbon sources for the production of PHAs. A vital finding of this study was the yield obtained by using plastic bags, i.e., 68.24 ± 0.27%. The effective use of plastic and lignocellulosic waste in the cultivation medium for the microbial production of PHA by a novel bacterial strain is discussed in the current study.

Development, characterization and evaluation of in-vitro anti-inflammatory activity of ginger extract based micro emulsion.

Zingeber officinale is a commonly used plant which has been shown to possess anti-inflammatory activity. The active compounds present in ginger are gingerols, shagaols and paradol. The aim of this study was formulation of topical microemulsion system to enhance the solubility and stability of ginger extract, as it is unstable in the presence of light, air, heat and long term storage, and to evaluate its anti-inflammatory activity. The solubility of ginger extract in different oils, surfactants, and co-surfactants was determined in order to find the optimal components for microemulsion. IPM was selected as oil phase, tween 80 and PEG 400 were selected as surfactant and co-surfactant respectively based on highest solubility values. Pseudo-ternary phase diagram was constructed in order to find out the microemulsion region. The prepared microemulsions were evaluated for pH, viscosity, conductivity, refractive index, globular size, zeta potential, polydispersity index, ginger extract content. The formulation F1 showed best physicochemical properties with smallest globular size. It also showed significant (p<0.05) anti-inflammatory effect as compared to reference piroxicam drug solution. Based on the results, it is concluded that ginger extract can be used to develop stable microemulsion system and promising anti-inflammatory activity.

Phenolic contents, antimicrobial and antioxidant activity of Olea ferruginea Royle (Oleaceae).

BACKGROUND: Olea ferruginea Royle (Oleaceae) has long been used as an important ethnomedicinal plant to cure fever and debility, toothache, hoarseness, throatache and skeleton disorders. In this study, phenolic contents, antimicrobial and antioxidant activities of leaf and bark extracts (chloroform, ethanol and methanol) of O. ferruginea were evaluated. METHODS: Total phenolic contents were determined by Folin-Ciocalteu Spectrophotometric method. Antimicrobial activity was examined against Bacillus subtilis and Staphylococcus aureus (Gram positive), Escherichia coli (Gram negative), Candida albicans and Sccharomyces cerevisiae (yeas strains) by disc diffusion method. Antioxidant activity was observed through DPPH assay. RESULTS: The higher phenolic content was found in bark extract (376 µg/mg) of O. ferruginea. Chloroform extracts was found inactive against tested microorganisms while ethanol and methanol extracts showed pronounced inhibitory activity against both gram positive and gram negative bacteria. Only methanol extract of leaves inhibited the yeast strains. None of the bark extract inhibited the growth of tested yeast strains. The zones of inhibition formed by plant extracts were compared with zones of inhibition of available reference antibiotic discs such as tetracycline, ciprofloxacin and nystatin. Higher antioxidant activity was observed with methanol extracts of leaves and bark of O. ferruginea. CONCLUSION: These findings show that O. ferruginea has potential antimicrobial and antioxidant activities. This study suggests a possible application of olive leaves and bark as sources of natural antimicrobial and antioxidants.

Anti-Cancerous Potential of Polyphenol-Loaded Polymeric Nanotherapeutics.

Recent evidence has extensively demonstrated the anticancer potential of nutraceuticals, including plant polyphenols. Polymeric nanocarrier systems have played an important role in improving the physicochemical and pharmacological properties of polyphenols, thus ameliorating their therapeutic effectiveness. This article summarizes the benefits and shortcomings of various polymeric systems developed for the delivery of polyphenols in cancer therapy and reveals some ideas for future work.

PREVALENCE OF HEPATITIS C IN DIABETIC PATIENTS: A PROSPECTIVE STUDY.

There is a strong evidence of the relationship between diabetes and hepatitis C however, there are certain gaps in the literature. Therefore, this study was carried out to determine the prevalence of hepatitis C in diabetic patients and risk factors associated with it, to evaluate the presence of possible relationship between hepatitis C and diabetes. Serological testing for anti HCV antibody was carried out on a sample of 100 diabetic patients visiting the diabetic clinic Nishtar Medical College and Hospital Multan. An anti HCV antibody test was carried out on HCV ELISA 3.0 (third generation) kit, locally purchased. Data about demographic information and history of risk factors for HCV was collected from diabetic patients using a structured questionnaire as an experimental tool, after taking informed consent. Data of about 100 non diabetic subjects (volunteer blood donors) was taken from the blood bank of that hospital. Prevalence rate of HCV infection among diabetic patients was recorded 19% and in the control group (non-diabetics) was 3%. Prevalence of HCV infection is higher in type 2 diabetic patients as compared to type 1 diabetic patients (84% vs. 16%). Diabetic patients between age group 46-55 years of age has high prevalence rates (47%) as compared to healthy individuals. Female diabetic patients have higher seropositivity (74%) as compared to male diabetic patients (26%). High prevalence of HCV infection has been reported among diabetic patients with duration of disease = 11 years (47%). Most of the patients were married (95%) and from urban locality (89%) and almost all were poor (99%). HCV positive diabetic patients have also history of blood transfusion (16%), hospital admissions (84%), major surgical procedure (63%), family history of hepatitis C (16%), razor sharing among males (16%) and comb sharing (79%). There was not any I/V drug addict (or history of I/V drug addiction), and tattooing, nose/ear piercing from contaminated needle and toothbrush sharing have not been seen among the participants of research.The results showed that in the present study the prevalence of HCV infection is six times higher in diabetic patients as compared to non-diabetic subjects (control group).

Permeation study through bacterial cellulose membrane.

Abstract: The objective of this study was to fabricate topical formulations of diclofenac diethylamine (DD) using isopropyl myristate (IPM) and isopropyl palmitate (IPP) as permeation enhancers. Franz cell and bacterial cellulose were used as analytical instrument and diffusion membrane, respectively. Permeation enhancers exhibited significant effect on the permeation characteristics of DD. It was concluded from the results that improved permeation of DD was observed when IPP was used as enhancer.

Formulation and characterization of glipizide solid dosage form with enhanced solubility.

Glipizide, a poor water-soluble drug belongs to BCS class II. The proposed work aimed to enhance the solubility of glipizide by preparing solid dispersions, using polyvinyl pyrrolidone (PVP) and polyethylene glycol (PEG). Solvent evaporation method was used for the preparation of glipizide solid dispersions. Solid dispersions were prepared in four different drug-to-polymer ratios i.e. 1:1, 1:2, 1:3 and 1:4. Mainly effect of three polymers (PVP K30, PVP K90 and PEG 6000) was evaluated on the solubility and dissolution of glipizide. The in-vitro dissolution of all prepared formulations was performed under pH 6.8 at 37°C using USP type II apparatus. In-vitro dissolution results revealed that the formulations having high concentrations of the polymer showed enhanced solubility. Enhancements in the solubility and rate of dissolution of the drug were noted in solid dispersion formulations compared to the physical blends and pure drug. Solid dispersions containing polyvinyl pyrrolidone exhibited a more favorable pattern of drug release compared to the corresponding solid dispersions with PEG. An increase in the maximum solubility of the drug within the solid dispersion systems was observed in all instances. Two solid dispersion formulations were optimized and formulated into immediate-release tablets, which passed all the pharmacopoeial and non-pharmacopoeial tests. Fourier transformed Infrared (FTIR) spectroscopy X-ray diffraction (XRD) and Differential scanning calorimetry (DSC) were used to indicate drug: polymer interactions in solid state. Analysis of the solid dispersion samples through characterization tests indicated the compatibility between the drug and the polymer.

Development of in vitro-in vivo correlation for encapsulated metoprolol tartrate.

This study was aimed to develop level A, B and C in vitro-in vivo correlation (IVIVC) for encapsulated metoprolol tartrate (T1, T2 and T3 having metoprolol tartrate/polymer ratio of 1: 1, 1: 1.5 and 1: 2,w/w). The in vitro data were correlated with in vivo data. For level A IVIVC, drug absorption data were calculated using Wagner-Nelson method. In addition, convolution approach was used to approximate plasma drug levels from in vitro dissolution data. The coefficient of determination (R2) for level A IVIVC was 0.720, 0.905, 0.928 and 0.878 for Mepressor, T1, T2 andT3 formulations, respectively, with acceptable percent error (< 15%). The value of R2 for level B and C IVIVC was 0.231and 0.714, respectively. It is also concluded that level A IVIVC is a proficient mathematical model for biowaiver studies involving study parameters as those implemented for T1S (T1formulation tested for dissolution in the presence of sodium lauryl sulfate) revealing that IVIVC level A is dosage form specific, rather than to be drug specific.

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.

Fabrication of solid lipid nanoparticles-based patches of paroxetine and their ex-vivo permeation behaviour.

Paroxetine is not suitable for oral administration due to its extensive first-pass metabolism, thus resulting in less bioavailability. This study aimed to prepare novel paroxetine-loaded solid lipid nanoparticles (SLNs) based sustained-release transdermal patches to overcome these problems by enhancing drug absorption and bioavailability. Nine formulations of paroxetine SLNs were prepared by the hot melt-homogenization method using different concentrations of glycerol monostearate (Kolliwax) and Tween 80. Then these prepared SLNs were incorporated in a matrix type transdermal patch having a matrix of ethyl cellulose and polyvinyl pyrrolidone in 3:2 with polyvinyl alcohol. The SLNs showed a particle size range of 113-230 nm and an entrapment efficiency of 85.14%. The SLNs showed sustained paroxetine release (77.86-95.63% release) up to 48 h. FTIR studies showed no interaction between drug and formulation components. Paroxetine is evenly distributed in an amorphous form in SLNs, as demonstrated by DSC as well as PXRD analysis. SLNs formulated patches showed higher drug permeation through the skin than drug-based transdermal patches., Draize patch test revealed no sign of erythema after applying paroxetine-loaded SLN patches (score 0) as observed with the marketed product. The developed SLNs based transdermal patches showed increased permeability and sustained release behaviour.

Ethylcellulose microparticles: a review.

Ethylcellulose (EC) based microencapsulated drug delivery systems are being extensively studied throughout the world for achieving extended drug release and protecting the core substance from degradation. The in vitro evaluation of EC microcapsules have elucidated that their particle characteristics are very useful to control drug release behavior, since these enable drugs to be released at a certain controlled release rate based on the characteristics of drug-EC linkage. This review encompasses microencapsulation techniques, core substances and other fundamentals involved in the preparation and characterization of EC microcapsules. EC microcapsules can be considered as mini-osmotic pumps. The release kinetics for EC microcapsules can be fine-tuned by altering osmolality of the dissolution medium or formulations and EC film mechanical characteristics by selecting appropriate EC molecular weights (viscosity), EC substitution grades, coating weights, and pore formers.

Eudragit FS based colonic microparticls of metoprolol tartrate.

Metoprolol, a cardioselective ß-blocker, is well absorbed in colon after oral administration with mean elimination half life of 3 h with bioavailability 50% due to extensive first pass effect, thus it was aimed to develop its modified release dosage form to reduce dosing frequency. Metoprolol tartrate loaded Eudragit FS microparticles were formulated using solvent evaporation technique by varying polymer contents and then compressing into tablets. The dissolution test was performed in simulated gastrointestinal fluid. All tabletted microparticles were tested for stability after storage in accelerated conditions. As a result of various analytical tests like FTIR, XRD and DSC analyses, drug was found stable in the microparticles. Metoprolol tartrate loaded Eudragit FS tabletted microparticles were stable in accelerated storage conditions. The release behavior of pH-dependent formulations was affected by the dissolution medium pH and the concentration of polymer used. There was a decrease in drug release rate with the increase in polymer concentration. In vitro drug release data (except test formulation F3) were best fitted to zero order model, which indicated the controlled release nature of formulation, while the Korsmeyer-Peppas model explored that drug release occurred according to case II relaxation transport mechanism (n > 0.89). Based on the results, it can be concluded that Eudragit FS is a suitable polymer to design pH dependent microparticles using solvent evaporation technique for the release of drug in colon and T2 can be considered as an optimum formulation on the basis of model independent (f2 test) kinetic interpretation of dissolution results (f2 < 50 for T2 versus reference).

Formulation development and in vitro evaluation of theophylline microcapsules.

The study was aimed to investigate microencapsulation of theophylline using different ratios of eudragit S 100 as wall material by the emulsion solvent evaporation technique. The release profiles, effect of stirring speed and different pH of dissolution medium on release profiles and stability were also studied. Various formulations of microcapsules were compressed in to tablets. In vitro dissolution studies indicated that the rate of drug release was reduced with an increase in the amount of Eudragit S 100. Moreover, the release data of various formulations were fitted to Zero order, First order, Higuchi, Hixson Crowell and Korsmeyer Peppas kinetic models. It was observed that the release of drug from all the formulations followed Higuchi's kinetic model as its value of coefficient of determination is greater than that of others. The release profiles of the test formulation in distilled water and various pH media were compared and decreased release rate was seen at lower pH i.e. pH 1.0. Slight or no change was apparent in the release rate at higher stirring speed compared to lower stirring speed. No significant changes were also observed in the drug release profiles of test tablets stored at different temperatures. Test tablet (F2) was found to produce similar and sustainable release rate compared to commercial product, Quibron-T/SR tablet on the basis of their T(70%). Similarly, f(2) values of reference versus F2 is 66.98 which show less difference between these two as compared to the comparison of reference with F1 and F3.

Development, characterization and In-vitro evaluation of guar gum based new polymeric matrices for controlled delivery using metformin HCl as model drug.

Currently, hydrogels are considered as ideal biomaterials due to their unique structure and characteristics that facilitates considerable hydrophilicity, swelling, drug loading and release. In this study, we report pH-responsive GG-MAA-AMPS hydrogel delivery system prepared via free radical polymerization technique. Hydrogels were loaded with Metformin HCl as a model drug. Hydrogels were characterized through Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and scanning electron microscopy (SEM). FTIR confirmed the successful crosslinking of reactants, hydrogel network formation and drug loading. TGA and DSC proved the higher thermal stability of reactants after crosslinking and drug loading. XRD analysis showed decrease in crystallinity of drug after loading into the hydrogels. SEM revealed smooth and glassy appearance of both loaded and unloaded hydrogels. Gel content was increased with increase in concentration of reactants. Drug entrapment was decreased by increasing concentration of GG and AMPS while MAA acted inversely. Hydrogels displayed pH-dependent swelling and drug release behavior being high at pH 6.8 and 7.4 while low at acidic pH (1.2). Oral tolerability in rabbits showed that hydrogels were safe without causing any hematological or histopathological changes in healthy rabbits. Based on the obtained results, GG-MAA-AMPS can be considered as potential carrier for metformin HCl as well as other hydrophilic drugs.

Determination of glycated albumin in serum and saliva by capillary electrophoresis utilizing affinity of 3-acrylamido phenylboronic acid selected by virtual screening and molecular docking.

The glycated albumin (G-alb) is a potential marker of hyperglycemia in diabetes and other neurodegenerative disorders in humans. G-alb's presence in the total human serum albumin (tHSA) is an important indicator in the timely diagnosis of disease. To identify G-alb content, it needs to be isolated from non-glycated albumin (NG-alb). Here, we present Capillary electrophoresis (CE) methods with 3-acrylamido phenylboronic acid (3-APBA) as an entrapped ligand in the agarose gel to develop agarose-3-APBA functional capillary and as an affinity ligand added to the buffer without agarose. 3-APBA was selected by computational virtual screening of several phenylboronic acid (PBA) compounds and other ligands to bind G-alb and separate from NG-alb selectively. The agarose-3-APBA functional capillary method involved agarose gel dilution approach coupled with injection pressure to obtain reduced viscosity and sufficient injection volume of protein samples. The method delivered separation in 9.7 min, with a resolution of 3.4, G-alb recovery up to 65%, and took 25 min to complete the entire process. The second method involved 3-APBA as an affinity ligand in the buffer and delivered separation in 4.2 min, with a resolution of 6.4, G-alb recovery up to 102% recovery, with relatively easy procedures. Therefore, it was further applied to determine G-alb content from tHSA in human serum and saliva. The G-alb found content in serum samples was in the range of 21. 1 ± ± 1.4% to 40.5  ± 1.6% out of tHSA and 25.1  ± 1.6% to 33.3 1.4% in saliva. The binding mechanisms were investigated by molecular dockings, which revealed hydrogen bonding, π-π, and van der walls interactions between 3-APBA and G-alb. The affinity was validated by affinity capillary electrophoresis (ACE), which revealed relatively strong interactions between 3-APBA and G-alb with the binding constant (Kb) of 4.53 × 109M - 1 to the 3.41 × 108M - 1 of 3-APBA and NG-alb. The affinity of 3-APBA toward G-alb was increased at pH 9.0 of the borax-borate (BB) buffer as background electrolyte (BGE). The limit of detection (LOD) was 10 nM, repeatability (RSD, n = 3) ≤ 1.4%, and recovery rate was 87.8 ± 1.6 to 100 ± 1.4% in serum and 97.3 ± 1.3 to 102.6 ± 1.1% in saliva. The sensitivity and reproducibility of the method met the detection requirements.

Potential of Nanocarrier-Based Drug Delivery Systems for Brain Targeting: A Current Review of Literature.

The advent of nanotechnologies such as nanocarriers and nanotherapeutics has changed the treatment strategy and developed a more efficacious novel drug delivery system. Various drug delivery systems are focused on drug-targeting of brain cells. However, the manifestation of the brain barrier is the main hurdle for the effective delivery of chemotherapeutics, ultimately causing treatment failure of various drugs. To solve this problem, various nanocarrier-based drug delivery system has been developed for brain targeting. This review outlines nanocarrier-based composites for different brain diseases and highlights nanocarriers for drug targeting towards brain cells. It also summarizes the latest developments in nanocarrier-based delivery systems containing liposomal systems, dendrimers, polymeric micelles, polymeric nanocarriers, quantum dots (QDs), and gold nanoparticles. Besides, the optimal properties of nanocarriers and therapeutic implications for brain targeting have been extensively studied. Finally, the potential applications and research opportunities for nanocarriers in brain targeting are discussed.

Quantitative Ethnobotanical Analysis of Medicinal Plants of High-Temperature Areas of Southern Punjab, Pakistan.

Lack of proper infrastructure and the poor economic conditions of rural communities make them dependent on herbal medicines. Thus, there is a need to obtain and conserve the historic and traditional knowledge about the medicinal importance of different plants found in different areas of the world. In this regard, a field study was conducted to document the medicinal importance of local plants commonly used by the inhabitants of very old historic villages in Southern Punjab, Pakistan. In total, 58 plant species were explored, which belonged to 28 taxonomic families, as informed by 200 experienced respondents in the study area. The vernacular name, voucher number, plant parts used, and medicinal values were also documented for each species. Among the documented species, Poaceae remained the most predominant family, followed by Solanaceae and Asteraceae. The local communities were dependent on medicinal plants for daily curing of several ailments, including asthma, common cold, sore throat, fever, cardiovascular diseases, and digestive disorders. Among the reported species, leaves and the whole plant remained the most commonly utilized plant parts, while extracts (38.8%) and pastes (23.9%) were the most popular modes of utilization. Based on the ICF value, the highest value was accounted for wound healing (0.87), followed by skincare, nails, hair, and teeth disorders (0.85). The highest RFC value was represented by Acacia nilotica and Triticum aestivum (0.95 each), followed by Azadirachta indica (0.91). The highest UV was represented by Conyza canadensis and Cuscuta reflexa (0.58 each), followed by Xanthium strumarium (0.37). As far as FL was concerned, the highest value was recorded in the case of Azadirachta indica (93.4%) for blood purification and Acacia nilotica (91.1%) for sexual disorders. In conclusion, the local inhabitants primarily focus on medicinal plants for the treatment of different diseases in the very old historic villages of Southern Punjab, Pakistan. Moreover, there were various plants in the study area that have great ethnobotanical potential to treat various diseases, as revealed through different indices.

In vitro-in vivo correlation study on nimesulide loaded hydroxypropylmethylcellulose microparticles.

This study involves mathematical simulation model such as in vitro-in vivo correlation (IVIVC) development for various extended release formulations of nimesulide loaded hydroxypropylmethylcellulose (HPMC) microparticles (M1, M2 and M3 containing 1, 2, and 3 g HPMC, respectively and 1 g drug in each) having variable release characteristics. In vitro dissolution data of these formulations were correlated to their relevant in vivo absorption profiles followed by predictability worth analysis of these Level A IVIVC. Nimaran was used as control formulation to validate developed formulations and their respective models. The regression coefficients of IVIVC plots for M1, M2, M3 and Nimaran were 0.834 9, 0.831 2, 0.927 2 and 0.898 1, respectively. The internal prediction error for all formulations was within limits, i.e., < 10%. A good IVIVC was found for controlled release nimesulide loaded HPMC floating M3 microparticles. In other words, this mathematical simulation model is best fit for biowaiver studies which involves study parameters as those adopted for M3 because the value of its IVIVC regression coefficient is the closest to 1 as compared to M1 and M2.

Formulation of two-drug controlled release non-biodegradable microparticles for potential treatment of muscles pain and spasm and their simultaneous spectrophotometeric estimation.

The objective of this study was to formulate stable and controlled release microparticles for simultaneous delivery and UV spectrophotometric detection in combined dosage of an non-steroidal anti-inflammatory drug (NSAID) (nimesulide, NMS) and a spasmolytic agent (tizanidine, TZN) to maintain plasma concentration that may increase patients compliance, improved therapeutic efficacy, The aim was also to reduce severity of upper GI side effects of NMS because of alteration in delivery pattern via slow release of drug from microparticles and to increase the benefits of spasticity and disability for spastic patients by administering TZN in a modified release formulation as these two drugs are often prescribed in combination for the management of pain associated with muscles spasm. Ethyl cellulose was used as a retardant polymer. Drug-polymer and drug-drug compatibility study were conducted by different analytical tests. Microparticles were prepared by coacervation thermal change method. The prepared microparticles were characterized for their micromeritics and drug loading. The prepared microparticles were light yellow, free flowing and spherical in shape. The drug-loaded microparticles showed 87% and 91% entrapment efficiency of NMS and TZN, respectively, and release was extended up to 10 h. The infrared spectra, differential scanning calorimetry thermograms and XRD spectra showed the stable character of both the drugs in the drug-loaded microparticles. The in vitro release study of microparticles was performed in phosphate buffer pH 6.8. Linearity was observed in the concentration range of 5.0-30.0 microg/mL of NMS and 0.5-3.0 microg/mL of TZN. The microparticles have a potential for the prolongation and simultaneous delivery of the NIM and TIZ. The proposed UV method for simultaneous detection can be used for routine analysis of combined dosage form.

Development and in vitro Evaluation of Gastro-protective Aceclofenac-loaded Self-emulsifying Drug Delivery System.

AIM: Chronic use of oral nonsteroidal anti-inflammatory drugs (NSAIDs) is commonly associated with gastric irritation and gastric ulceration. Therefore, the aim of study was to develop a novel oral drug delivery system with minimum gastric effects and improved dissolution rate for aceclofenac (ACF), a model BCS class-II drug. METHODS: Self-emulsifying drug delivery systems (SEDDS) were formulated to increase the solubility and ultimately the oral bioavailability of ACF. Oleic acid was used as an oil phase, Tween 80 (T80) and Kolliphor EL (KEL) were used as surfactants, whereas, polyethylene glycol 400 (PEG 400) and propylene glycol (PG) were employed as co-surfactants. Optimized formulations (F1, F2, F3 and F4) were analyzed for droplet size, poly dispersity index (PDI), cell viability studies, in vitro dissolution in both simulated gastric fluid and simulated intestinal fluid, ex vivo permeation studies and thermodynamic stability. RESULTS: The optimized formulations showed mean droplet sizes in the range of 111.3 ± 3.2 nm and 470.9 ± 12.52 nm, PDI from 244.6 nm to 389.4 ± 6.51 and zeta-potential from -33 ± 4.86 mV to -38.5 ± 5.15 mV. Cell viability studies support the safety profile of all formulations for oral administration. The in vitro dissolution studies and ex vivo permeation analysis revealed significantly improved drug release ranging from 95.68 ± 0.02% to 98.15 ± 0.71% when compared with control. The thermodynamic stability studies confirmed that all formulations remain active and stable for a longer period. CONCLUSION: In conclusion, development of oral SEDDS might be a promising tool to improve the dissolution of BCS class-II drugs along with significantly reduced exposure to gastric mucosa.