Response surface methodology was employed to study the effect of formulation composition variables, water content (60%-80%, w/w) and oil and surfactant (O/S) ratio (0.17-1.33), as well as high-shear emulsification conditions, mixing rate (300-3,000 rpm) and mixing time (5-30 minutes) on the properties of sodium diclofenac-loaded palm kernel oil esters-nanoemulsions. The two response variables were droplet size and viscosity. Optimization of the conditions according to the four variables was performed for preparation of the nanoemulsions with the minimum values of particle size and viscosity. The results showed that the experimental data could be sufficiently fitted into a third-order polynomial model with multiple regression coefficients (R(2) ) of 0.938 and 0.994 for the particle size and viscosity, respectively. Water content, O/S ratio and mixing time, quadrics of all independent variables, interaction between O/S ratio and mixing rate and between mixing time and rate, as well as cubic term of water content had a significant effect (P<0.05) on the particle size of nanoemulsions. The linear effect of all independent variables, quadrics of water content and O/S ratio, interaction of water content and O/S ratio, as well as cubic term of water content and O/S ratio had significant effects (P<0.05) on the viscosity of all nanoemulsions. The optimum conditions for preparation of sodium diclofenac nanoemulsions were predicted to be: 71.36% water content; 0.69 O/S ratio; 950 rpm mixing rate, and 5 minute mixing time. The optimized formulation showed good storage stability in different temperatures.
One of the popular approaches in controlling drug delivery from the polymeric carriers is suitably achieved by the inclusion of crosslinking agents into the formulations at different concentrations. Nevertheless, addition of the chemical crosslinkers such as glutaraldehyde, formaldehyde etc, used in the drug delivery systems causes very serious cytotoxic reactions. These chemical crosslinking agents did not offer any significant advantageous effects when compared to the natural crosslinking agents for instance genipin, which is quite less toxic, biocompatible and offers very stable crosslinked products. Based on the earlier reports the safety of this particular natural crosslinker is very well established, since it has been widely used as a Chinese traditional medicine for long-time, isolated from fruits of the plant Gardenia jasminoides Ellis. This concise article largely portrayed the value of this unique natural crosslinker, utilized in controlling the drug delivery from the various formulations.
Capillary electrophoresis coupled with a capacitively coupled contactless conductivity detector (CE-C(4)D) has been employed for the determination of the β-blocker drugs (atenolol and amiloride) in pharmaceutical formulations. 150 mM acetic acid was used as background electrolyte. The influence of several factors (detector excitation voltage and frequency, buffer concentration, applied voltage, capillary temperature, and injection time) was studied. Non-UV absorbing L-valine was used as an internal standard; the analytes were all separated in less than 7 min. The separation was carried out in normal polarity mode at 28 °C, 25 kV, and using hydrodynamic injection (25 s). The separation was effected in a bare fused-silica capillary 75 μm × 52 cm. The CE-C(4)D method was validated with respect to linearity, limit of detection and quantification, accuracy, precision, and selectivity. Calibration curves were linear over the range 5-250 μg mL(-1) for the studied analytes. The relative standard deviations of intra- and inter-day precisions of migration times and corrected peak areas were less than 6.0%. The method showed good precision and accuracy and was successfully applied to the simultaneous determination of the β-blocker drugs in different pharmaceutical tablets.
The aim of the present study is to formulate and investigate the potential of nanoemulsion formulation for topical delivery of ketoprofen. In this study, Palm Oil Esters (POEs) a newly introduced oil by Universiti Putra Malaysia researchers was chosen for the oil phase of the nanoemulsion, because the oil was reported to be a good vehicle for pharmaceutical use. Oil-in-water nanoemulsion was prepared by spontaneous emulsification method. The droplets size was studied by laser scattering spectroscopy (Nanophox) and Transmission Electron Microscopy (TEM). Franz diffusion cells were used, to determine the drug release and drug transferred through methyl acetate cellulose membrane (artificial membrane). The results of droplets size analysis shows the droplets are in the range of nanoemulsion which is below than 500 nm. The in vitro release profile shows a sufficient percentage of drugs released through the methyl acetate cellulose membrane. This initial study showed that the nanoemulsion formulated using POEs has great potential for topical delivery of ketoprofen.
A capillary electrophoresis (CE) method has been developed that allows the separation and estimation of primaquine enantiomers using hydroxypropyl-gamma-cyclodextrin (HP-gamma -CD) as a chiral selector. The influence of chemical and instrumental parameters on the separation, such as type and concentration of CD, buffer concentration, buffer pH, applied voltage, capillary temperature, and injection time, were investigated. Good separation of the racemic mixture of primaquine was achieved using a fused-silica capillary (52.5 cm effective length x 50 microm id) and a background electrolyte composed of tris-phosphate buffer solution (50 mM, pH 2.5) containing 15 mM HP-gamma-CD as a chiral selector. The recommended applied voltage, capillary temperature, and injection time were 15 kV, 25 degrees C, and 6 s, respectively. Within-day and interday reproducibility of peak area and migration time gave relative standard deviation values ranging from 1.05-3.30%. Good recoveries (range of 96.8-104.9%) were obtained from the determination of placebos that were spiked with 0.25-1.00 mg/L primaquine. The proposed CE method was successfully applied to the assay of primaquine diphosphate in pharmaceutical formulations (tablets).
Prevention of cardiovascular disease by modifying its major risk factors, including serum cholesterol levels, is an important strategy. Regular intake of garlic has been suggested, but its impact on cholesterol levels has been inconsistent.
The present study is an attempt to formulate a controlled-release matrix tablet formulation for alfuzosin hydrochloride by using low viscous hydroxy propyl methyl cellulose (HPMC K-100 and HPMC 15cps) and its comparison with marketed product. Different batches of tablets containing 10 mg of alfuzosin were prepared by direct compression technique and evaluated for their physical properties, drug content, and in vitro drug release. All the formulations had a good physical integrity, and the drug content between the batches did not vary by more than 1%. Drug release from the matrix tablets was carried out for 12 hr and showed that the release rate was not highly significant with different ratios of HPMC K-100 and HPMC15cps. Similar dissolution profiles were observed between formulation F3 and the marketed product throughout the study period. The calculated regression coefficients showed a higher r2 value with zero-order kinetics and Higuchi model in all the cases. Although both the models could be applicable, zero-order kinetics seems to be better. Hence, it can be concluded that the use of low viscous hydrophilic polymer of different grades (HPMC K-100 and HPMC 15cps) can control the alfuzosin release for a period of 12 hr and was comparable to the marketed product.
Response surface methodology (RSM) was utilized to investigate the influence of the main emulsion composition; mixture of palm and medium-chain triglyceride (MCT) oil (6%-12% w/w), lecithin (1%-3% w/w), and Cremophor EL (0.5%-1.5% w/w) as well as the preparation method; addition rate (2-20 mL/min), on the physicochemical properties of palm-based nanoemulsions. The response variables were the three main emulsion properties; particle size, zeta potential and polydispersity index. Optimization of the four independent variables was carried out to obtain an optimum level palm-based nanoemulsion with desirable characteristics. The response surface analysis showed that the variation in the three responses could be depicted as a quadratic function of the main composition of the emulsion and the preparation method. The experimental data could be fitted sufficiently well into a second-order polynomial model. The optimized formulation was stable for six months at 4 °C.
Galantamine hydrobromide is formulated in tablets and capsules prescribed through oral delivery for the treatment of Alzheimer's disease. However, oral delivery of drugs can cause severe side effects such as nausea, vomiting, and gastrointestinal disturbance. Transdermal delivery of galantamine hydrobromide could avoid these unwanted side effects. In this work, galantamine hydrobromide was formulated in gel drug reservoir which was then fabricated in the transdermal patch. The in vitro drug release studies revealed that the drug release from the donor chamber to receptor chamber of Franz diffusion cell was affected by the amount of polymer, amount of neutralizer, amount of drug, types of permeation enhancer, and amount of permeation enhancer. Visual observations of the gels showed that all formulated gels are translucent, homogeneous, smooth, and stable. These gels have pH in the suitable range for skin. The gel also showed high drug content uniformity. Hence, this formulation can be further used in the preparation of transdermal patch drug delivery system.
To investigate and compare the effect of three analytical methods, hydrogen bromide titrimetry (HBr titrimetry), infrared spectroscopy (IR spectroscopy), and first derivative UV-spectrophotometry (FDUV-spectrophotometry) in the determination of degree of deacetylation (DD) of chitosan.
The aims of the present research were to mask the intensely bitter taste of sumatriptan succinate and to formulate orally disintegrating tablets (ODTs) of the taste masked drug. Taste masking was performed by coating sumatriptan succinate with Eudragit EPO using spray drying technique. The resultant microspheres were evaluated for thermal analysis, yield, particle size, entrapment efficiency and in vitro taste masking. The tablets were formulated by mixing the taste masked microspheres with different types and concentrations of superdisintegrants and compressed using direct compression method followed by sublimation technique. The prepared tablets were evaluated for weight variation, thickness, hardness, friability, drug content, water content, in vitro disintegration time and in vitro drug release. All the tablet formulations disintegrated in vitro within 37-410 s. The optimized formulation containing 5% Kollidon CL-SF released more than 90% of the drug within 15 min and the release was comparable to that of commercial product (Suminat®). In human volunteers, the optimized formulation was found to have a pleasant taste and mouth feel and disintegrated in the oral cavity within 41 s. The optimized formulation was found to be stable and bioequivalent with Suminat®.
Conventional melt pelletization and granulation processes produce round and dense, and irregularly shaped but porous agglomerates respectively. This study aimed to design centrifugal air-assisted melt agglomeration technology for manufacture of spherical and yet porous "granulets" for ease of downstream manufacturing and enhancing drug release. A bladeless agglomerator, which utilized shear-free air stream to mass the powder mixture of lactose filler, polyethylene glycol binder and poorly water-soluble tolbutamide drug into "granulets", was developed. The inclination angle and number of vane, air-impermeable surface area of air guide, processing temperature, binder content and molecular weight were investigated with reference to "granulet" size, shape, texture and drug release properties. Unlike fluid-bed melt agglomeration with vertical processing air flow, the air stream in the present technology moved centrifugally to roll the processing mass into spherical but porous "granulets" with a drug release propensity higher than physical powder mixture, unprocessed drug and dense pellets prepared using high shear mixer. The fast-release attribute of "granulets" was ascribed to porous matrix formed with a high level of polyethylene glycol as solubilizer. The agglomeration and drug release outcomes of centrifugal air-assisted technology are unmet by the existing high shear and fluid-bed melt agglomeration techniques.
The human small intestine, with its enormous absorptive surface area, is invariably the principal site of drug absorption. Hence, the residence time of a dosage form in this part of the gut can have a great influence on the absorption of the contained drug. Various methods have been employed to monitor the gastrointestinal transit of pharmaceutical dosage forms, but the use of gamma-scintigraphy has superceded all the other methods. However, careful consideration of the time interval for image acquisition and proper analysis of the scintigraphic data are important for obtaining reliable results. Most studies reported the mean small intestinal transit time of various dosage forms to be about 3-4h, being closely similar to that of food and water. The value does not appear to be influenced by their physical state nor the presence of food, but the timing of food intake following administration of the dosage forms can influence the small intestinal transit time. While the mean small intestinal transit time is quite consistent among dosage forms and studies, individual values can vary widely. There are differing opinions regarding the effect of density and size of dosage forms on their small intestinal transit properties. Some common excipients employed in pharmaceutical formulations can affect the small intestinal transit and drug absorption. There is currently a lack of studies regarding the effects of excipients, as well as the timing of food intake on the small intestinal transit of dosage forms and drug absorption.
Diclofenac (DF) was first synthesized in the 1960's and is currently available as ophthalmic, oral, parenteral, rectal and skin preparations. This review focuses on the administration of DF to the skin. As a member of the non-steroidal anti-inflammatory (NSAID) group of drugs the primary indications of DF are for the management of inflammation and pain but it is also used to treat actinic keratosis. The specific aims of this paper are to: (i) provide an overview of the pharmacokinetics and metabolism of DF following oral and topical administration; (ii) examine critically the various formulation approaches which have been investigated to enhance dermal delivery of DF; and (iii) identify new formulation strategies for enhanced DF skin penetration.
A single dose study was conducted to evaluate the bioavailability of a novel self-emulsifying vitamin E preparation, in comparison with that of a commercial product, Natopherol, available as soft gelatin capsules under fasted condition. The self-emulsifying preparation achieved a faster rate and higher extent of absorption. A statistically significant difference was observed between the values of the two preparations in the parameters AUC, Cmax and Tmax. Moreover, the 90% confidence interval of the logarithmic transformed AUC values of the self-emulsifying preparation over those of the soft gelatin capsule product was found to be between 2.1 and 4.1, suggesting an increase in bioavailability of between 210 and 410%. As for Cmax, the 90% confidence interval was between 2.1 and 3.0. However, no statistically significant difference was observed between the t(1/2) values estimated from the plasma concentration versus time data of the two preparations. The values are also comparable to those reported in the literature.
In order to improve the membrane lipophilicity and the affinity towards the environment of lipid bilayers, squalene (SQ) could be conjugated to phospholipids in the formation of liposomes. The effect of membrane composition and concentrations on the degradation of liposomes prepared via the extrusion method was investigated. Liposomes were prepared using a mixture of SQ, cholesterol (CH) and Tween80 (TW80). Based on the optimal conditions, liposome batches were prepared in the absence and presence of SQ. Their physicochemical and stability behavior were evaluated as a function of liposome constituent. From the optimization study, the liposomal formulation containing 5% (w/w) mixed soy lecithin (ML), 0.5% (w/w) SQ, 0.3% (w/w) CH and 0.75% (w/w) TW80 had optimal physicochemical properties and displayed a unilamellar structure. Liposome prepared using the optimal formulation had a low particle size (158.31 ± 2.96 nm) and acceptable %increase in the particle size (15.09% ± 3.76%) and %trolox equivalent antioxidant capacity (%TEAC) loss (35.69% ± 0.72%) against UV light treatment (280-320 nm) for 6 h. The interesting outcome of this research was the association of naturally occurring substance SQ for size reduction without the extra input of energy or mechanical procedures, and improvement of vesicle stability and antioxidant activity of ML-based liposome. This study also demonstrated that the presence of SQ in the membrane might increase the acyl chain dynamics and decrease the viscosity of the dispersion, thereby limiting long-term stability of the liposome.
The objective of this research was to formulate an aerosol concentrate containing haruan (Channa
striatus) water extract that would produce a thin film when sprayed onto a wound and could be used for wound dressing. The aerosol concentrates were formulated with various polymer and plasticiser mixtures and tested in dispersion systems. The polymers evaluated were hydroxypropyl methylcellulose (HPMC), carboxymethylcellulose sodium (CMC Sodium), acacia, tragacanth, chitosan, gelatine and gelatine (bloom 151–160), all at concentrations of 2%. The plasticisers evaluated were polyethylene glycol (PEG) 400 and 4000, glycerine, propylene glycol, and triacetin. Films were prepared from film-forming dispersions by casting techniques. Film-forming dispersions were characterised in terms of pH, density, surface tension, rheological properties, particle size distribution, and tackiness. Based on these evaluations, HPMC was chosen as the best polymer. It produced a film with the expected qualities and was easy to reproduce in the form of dispersions or as thin transparent films. Glycerine was judged as the most appropriate plasticiser because it produced the concentrate having the desired qualities and properties expected from an aerosol concentrate.
Herein, self-assembled three-dimensional reduced graphene oxide (RGO)-based hydrogels were synthesized and characterized in detail. A thorough investigation on the uptake of three widely used pharmaceutical drugs, viz. Naproxen (NPX), Ibuprofen (IBP) and Diclofenac (DFC) was carried out from aqueous solutions. To ensure the sustainability of developed hydrogel assembly, practically important parameters such as desorption, recyclability and applicability to real samples were also evaluated. Using the developed 3D hydrogels as adsorptive platforms, excellent decontamination for the above mentioned persistent pharmaceutical drugs was achieved in acidic pH with a removal efficiency in the range of 70-80%. These hydrogels showed fast adsorption kinetics and experimental findings were fitted to different kinetic models, such as pseudo-first order, pseudo-second order, intra-particle and the Elovich models in an attempt to better understand the adsorption kinetics. Furthermore, equilibrium adsorption data was fitted to the Langmuir and Freundlich models, where relatively higher R2 values obtained in case of former one suggested that monolayer adsorption played an important part in drug uptake. Thermodynamic aspects were also studied and negative ΔG0 values obtained indicated the spontaneous nature of adsorption process. The study was also extended to check practical utility of as-prepared hydrogels by spiking real aqueous samples with drug solution, where high % recoveries obtained for NPX, IBP and DFC were of particular importance with regard to prospective application in wastewater treatment systems. We advocate RGO-based hydrogels as environmentally benign, readily recoverable/recyclable material with excellent adsorption capacity for application in wastewater purification.
Gelatin is widely used in pharmaceuticals as a protective coating, such as soft and hard capsule shells. However, the animal source of gelatin is a sensitive issue because certain gelatins such as porcine and bovine gelatins are not welcome in Halal, Kosher and Hindus' consumer goods. Recently, we have documented DNA barcoding and multiplex PCR platforms for discriminating porcine, bovine and fish gelatins in various fish and confectionary products; but those assays were not self-authenticating and also not tested in highly refined pharmaceutical products. To address this knowledge gap, here we report a self-authenticating multiplex PCR-restriction fragment length polymorphism (RFLP) assay to identify animal sources of various gelatin in pharmaceutical capsules. Three different restriction enzymes, BsaAI, Hpy188I and BcoDI were used to yield distinctive RFLP patterns for gelatin-based bovine (26, 94 bp), fish (97, 198 bp) and porcine (17, 70 bp) DNA in control experiments. The specificity was cross-tested against 16 non-target species and the optimised assay was used to screen gelatin sources in 30 halal-branded pharmaceuticals capsule shells. Bovine and porcine DNA was found in 27 and 3 of the 30 different capsules products. The assay was suitable for detecting 0.1 to 0.01 ng total DNA extracted from pure and mixed gelatins. The study might be useful to authenticate and monitor halal, kosher, vegetarian and Hindu compliant pharmaceuticals, foods and cosmetics.