Studies on self-nanoemulsifying drug delivery system of flurbiprofen employing long, medium and short chain triglycerides

The aim of the study was to successfully design, formulate and evaluate self-nanoemulsifying drug delivery system [SNEDDS] of poorly aqueous soluble drug viz. flurbiprofen using long [LCT], medium [MCT] and short chain triglycerides [SCT]. The SNEDDS are thermodynamically stable lipid based drug delivery systems which consist of mixture of oil, surfactant and co-surfactant. Upon aqueous dilution, this mixture produces nano-emulsion spontaneously on slight agitation. The excipients intended to be used were screened for their potential to dissolve the drug and to form clear dispersion upon aqueous dilution. Labrafil M 1944 CS, capryol-90 and triacetin were selected as long, medium and short chain triglycerides, respectively, as lipids while tween-80 and polyethylene glycol-400 [PEG-400]/ethanol [3:1 ratio] were selected as surfactant and co-surfactant, respectively. The excipients were studied at every possible combination ratios using pseudo-ternary diagram. The LCT, MCT and SCT-SNEDDS were optimized using thermodynamic studies, percentage transmittance value, viscosity, refractive index [RI], electrical conductivity, globule size analysis and in-vitro drug release studies. The drug release profiles of optimized SNEDDS were then compared with market product at different pH mediums. The LCT-SNEDDS was considered to be superior for enhancement of the drug bioavailability when compared with other SNEDDS formulations and market product

Controlled release matrix tablets of glipizide: influence of different grades of ethocel and Co-excipient on drug release

The aim of the current study was to formulate and evaluate glipizide controlled release matrix tablets by means of different grades of polymer Ethoceland different co-excipients in order to evaluate their effect on drug release profiles during in vitro dissolution studies. Type II diabetes mellitus is usually treated with Glipizide. Glipizide belongs to sulfonylurea group. Gastric disturbance and severe hypoglycemia has been observed after taking glipizide orally. To overcome these problems, controlled release matrices were developed using different grades of ethyl cellulose polymer with a drug-polymer ratio of 1: 3by the direct compression method. The effect on drug release of partial replacement of lactose by different co-excipients, HPMC K100M, starch and CMC, were also studied. Diameter, thickness, hardness, friability, weight variations, drug contents of formulations were tested, these properties were within prescribed limits. Co-excipients and polymer containing formulations were compared to the without co-excipients and polymer containing formulations with respect to their release profile. After a 24-hour release study, ethyl cellulose polymer containing formulation exhibited prolonged release for 5-16 hours; however the polymer Ethocel standard FP 7 Premium without co-excipient containing formulation exhibited controlled release for 24 hours. Incompatibility was investigated between drugs, co-excipient DSC and polymer study was performed and any type of interaction was not found. Different kinetic models were used to study the release mechanism. An enhanced release rate was observed in case of excipients containing formulations

To study the influence of different grades of Ethylcellulose ether derivative polymer Ethocel[registered] and co-excipient on drug release profile of controlled release matrix tablet of acarbose

The aim of the study presented is to formulate and evaluate Acarbose controlled release matrix tablets by means of different grades of polymer Ethocel and different co-excipients with the intention to see their effects on drug release profile during in vitro dissolution studies. Controlled release dosage forms is gaining rapid popularity due to its positive aspect of reduction in dosage frequency and curtailing side effects. Controlled released tablets of Acarbose were prepared by direct compression method, using Ethocel[registered sign] Standard 7 Premium and Ethocel[registered sign] Standard 7 FP premium polymer. The effect of co-excipients including hydroxypropyl methylcellulose [HPMC], Carboxymethyl cellulose [CMC] and starch on the drug placing 30% lactose were also examined. In-vitro studies were carried out with the help of phosphate buffer [PH 7.4] as dissolution medium. Drug release mechanism was assessed by applying various kinetic models. Similarly / dissimilarity factor f[2]/ f[1] were applied for determination of dissolution profile of the test and reference formulations. Physiochemical characteristics were in the USP satisfactory limits. Conventional Acarbose tablet released 97% of the drug within 2 hrs. Ethocel[registered sign] Standard 7 premium and Ethocel[registered sign] standard 7 FP released 59.9% and 47.01% of the drug within 6 and 99.9% and 97% within 24 hours, respectively. This effect possibly has been aceived owing to the smaller particle size of the Ethocel[registered sign] Standard 7 FP premium which show evidence of anomalous, nonfickian release kinetics. Co-excipients like HPMC, CMC and starch augment the drug release rates from the matrices which may be attributed to their hydrophilic nature. Ethocel[registered sign] Standard 7 Premium and Ethocel[registered sign] Standard premium 7 FP polymers show a promising response in fruitful production of controlled release tablets by direct compression method

Pharmacokinetic evaluation of ibuprofen controlled release matrix tablets using hydrophilic Eudragit® polymer and co-excipients

The present study was conducted to formulate controlled release dosage forms containing Ibuprofen with Eudragit® S 100 polymer. The tablets were formulated at three different ratios with the polymer to investigate the effect of different concentrations of polymer on in vitro drug release patterns/kinetics and in vivo absorption/pharmacokinetics. Pre-formulation studies were conducted including bulk density, tapped density, compressibility index, Hausner ratio and angle of repose. In vitro studies were conducted using phosphate buffer [pH 7.4] as dissolution medium. In vivo performance was evaluated using albino rabbits. Physico-chemical characteristics [i.e. dimensional tests, weight variation, hardness, friability and drug content determination] fell in the USP acceptable limits. The compressibility index was found to range between 12.02 +/- 0.01% and 18.66 +/- 0.03%, the Hausner ratio varied between 1.02 +/- 0.01 and 1.19 +/- 0.10 and the angle of repose ranged from 15.19 +/- 0.01 to 24.52 +/- 0.10, all indicating better flow properties than the bulk-reference standard. Both bulk and tapped densities also fell in the USP acceptable range. Ibuprofen market tablets showed T[max] of 2.1 +/- 0.4h, which was significantly [P-value <0.05] lower compared to that of the reference standard [i.e. 4.09 +/- 1.3h]. Ibuprofen test formulation has a half-life [T[1/2]] of 16.9 +/- 2.5h, which was significantly [P-value<0.001] higher compared to that of the reference standard [i.e. 9.23 +/- 2.9h]. Eudragit® S 100 polymers can be used efficiently to develop directly compressed prolonged release tablets

simple and rapid approach to evaluate the in vitro in vivo role of release controlling agent ethyl cellulose ether derivative polymer

Diclofenac sodium [DCL-Na] conventional oral tablets exhibit serious side effects when given for a longer period leading to noncompliance. Controlled release matrix tablets of diclofenac sodium were formulated using simple blending [F-1], solvent evaporation [F-2] and co-precipitation techniques [F-3]. Ethocel[R] Standard 7 FP Premium Polymer [15%] was used as a release controlling agent. Drug release study was conducted in 7.4 pH phosphate buffer solutions as dissolution medium in vitro. Pharmacokinetic parameters were evaluated using albino rabbits. Solvent evaporation technique was found to be the best release controlling technique thereby prolonging the release rate up to 24 hours. Accelerated stability studies of the optimized test formulation [F-2] did not show any significant change [p<0.05] in the physicochemical characteristics and release rate when stored for six months. A simple and rapid method was developed for DCL-Na active moiety using HPLC-UV at 276nm. The optimized test tablets [F-2] significantly [p<0.05] exhibited peaks plasma concentration [C[max]=237.66 +/- 1.98] and extended the peak time [t[max]=4.63 +/- 0.24]. Good in-vitro in vivo correlation was found [R[2] =0.9883] against drug absorption and drug release. The study showed that once-daily controlled release matrix tablets of DCL-Na were successfully developed using Ethocel[R] Standard 7 FP Premium

Formulation and in vitro evaluation of clotrimazole gel containing almond oil and tween 80 as penetration enhancer for topical application

Achieving a desirable percutaneous absorption of drug molecule is a major concern in formulating dermal and transdermal products. The use of penetration enhancers could provide a successful mean for this purpose. The aim of this study was to develop Clotrimazole gel and to evaluate the effect of almond oil and tween 80 [in different concentrations], on the permeation of drug through rabbit skin in vitro. In order to investigate the effect of penetration enhancers used in this study on the permeation of Clotrimazole through sections of excised rabbit skin, Franz diffusion cell was employed. Sample solution was withdrawn at specific time interval up to 24 h. Significant difference in permeation among the eight formulations was seen in the study. The permeation profile of various formulations also showed that the added enhancers in individual batches affected the permeation of the drug. Drug permeation increased with increased concentration of Tween 80 and decreased concentration of almond oil. Furthermore, almond oil combined with tween 80 showed synergistic effect. The clotrimazole gels were successfully formulated and could be beneficial for topical use

Synthesis, conjugation and evaluation of some novel polymers and their micro particles for sustained release drug formulations

To prepare and evaluate three novels functionalized polymers [PGA, PGA-co-caprolactone and PGA-copentadecalactone] for the development of nanoparticles which were further used in the development of a novel polymeric prodrug using Ibuprofen as a model drug. The Ibuprofen-polymer prodrug was developed by coupling the drug to one of the three prepared polyester polymers via ester linkage. A hydrolytic enzyme was used to prepare two polymer monomers, glycerol and polyvinyl adipate, which are non toxic, ester linked biological monomers. The polymers and their prodrug were characterized using NMR, GPC, UV-spectrophotometer and DSC. In vitro drug release study of Ibuprofen-polymer conjugate was performed in phosphate buffer PH 7.4 using a roller [Stuart STR 1] placed in an incubator [Stuart SI 60] and the temperature was kept constant at 37 +/- 1°C. Among the three polymers, glycerol-adipateco-pentadecalactone was observed to give a burst release following slow release in the medium. These characteristics suggest that these polymers can be successfully used in sustained release drug formulations

Development of novel diclofenac potassium controlled release tablets by wet granulation technique and the effect of co-excipients on in vitro drug release rates

The aim of the present study was the formulation and evaluation of controlled release polymeric tablets of Diclofenac Potassium by wet granulation method for the release rate, release pattern and the mechanism involved in drug release. Formulations having three grades of polymer Ethocel [7P; 7FP, 10P, 10FP, 100P, 100FP] in several drugs to polymer ratios [10:3 and 10:1] were compressed into tablets using wet granulation method. Co-excipients were added to some selected formulations to investigate their enhancement effect on in vitro drug release patterns. In vitro drug release studies were performed using USP Method-1 [Rotating Basket method] and Phosphate buffer [pH 7.4] was used as a dissolution medium. The similarities and dissimilarities of release profiles of test formulations with reference standard were checked using f2 similarity factor and f1 dissimilarity factor. Mathematical/Kinetic models were employed to determine the release mechanism and drug release kinetics

Development of a novel ketoprofen transdermal patch: effect of almond oil as penetration enhancers on in-vitro and ex-vivo penetration of ketoprofen through rabbit skin

The aim of the study was to formulate and evaluate topically applied ketoprofen gels and patches and to see the effect of naturally occurring almond oil as penetration enhancer on the penetration of ketoprofen through artificial membrane/rabbit skin. Prior to ketoprofen gel and patch formulation, the particle size and particle size determination of ketoprofen was analyzed by Particle size analyzer [Horiba LA300]. Ketoprofen gels and patches were formulated and almond oil was added in several concentrations i.e. 0.5%, 1%, 1.5%, 2%, 2.5% and 3%. The formulated gels were evaluated by several parameters like pH, spreadibility, consistency, homogeneity, skin irritation and drug content determination. In vitro drug permeation studies from transdermal gels and patches were carried out across artificial membrane and rabbit skin by using Franz Cell Apparatus [PermeGear, USA]. Kinetics model was employed to the release patterns of ketoprofen from gel and patches in order to investigate the drug transport mechanism. The cumulative amount of drug penetrated from different formulations was statistically evaluated by using One-way analysis of variance [ANOVA]. Stability study was performed for various batches of ketoprofen transdermal gel. Almond oil as penetration enhancer in various concentrations significantly enhances the penetration of drug from transdermal gels and patch across synthetic membrane/rabbit skin but was most significant when used in 3% concentration

Formulation development and investigation of ibuprofen controlled release tablets with hydrophilic polymers and the effect of co-excipients on drug release patterns

The aim and objective of the present study was to formulate and evaluate controlled release polymeric tablets of Ibuprofen with determinations of formulation factors using various grades and types of polymer Ethocel i.e. Ethocel Standard 10P; 10FP, 100P and 100FP for their release rates and release patterns in suitable media and also the mechanism involved in the release of drug from the matrices. The effect of several co-excipients was also studied on the drug release rates and patterns of Ibuprofen from the polymeric matrices. Ibuprofen-Ethocel CR tablets were prepared at three different D:P ratios i.e. 10:1, 10:2 and 10:3. The effects of co-excipients were studied only in formulations having D:P ratio of 10:3. In vitro drug release studies of Ibuprofen-Ethocel controlled release matrix tablets were carried out in phosphate buffer pH 6.8 using Pharma Test Dissolution Apparatus adopting Rotating Basket Method according to USP. Different kinetic models were applied to the release data of test formulations in order to investigate the release mechanism of drug from the controlled release matrix tablets. The release patterns of Ibuprofen-Ethocel CR matrices were compared with reference conventional Ibuprofen tablets and Ibuprofen SR tablets. F[2] similarity factor was applied to the test formulations and reference standard to compare their similarities. The drug formulations studied exhibited satisfactory release results

Effect of olive oil on transdermal penetration of flurbiprofen from topical gel as enhancer

The present study was conducted to formulate and evaluate flurbiprofen transdermal gel. A standard calibration curve was constructed to obtain a regression line equation to be used for finding out the concentration of drug in samples. Olive oil was used as penetration enhancer and was added in different concentrations to some selected formulations to see its enhancement effect on in vitro drug release profiles. The prepared gels were evaluated for several physico-chemical parameters to justify their suitability for topical use. The in vitro drug release studies were carried out by using Franz cell diffusion apparatus across both synthetic membrane and excised albino rabbit skin. In order to investigate the drug release mechanism a kinetic approach was made by employing Korsmeyer kinetic model to the in vitro drug release profiles of flurbiprofen. The flurbiprofen topical gels were successfully prepared and could be beneficial for topical use

Formulation and in vitro evaluation of ofloxacin-ethocel controlled release matrix tablets prepared by wet granulation method: influence of co-excipients on drug release rates

Being controlled release dosage forms, tablets allow an improved absorption and release profiles of Ofloxacin. The fact that drugs with fine particles size can be compressed well after wetting, so in our research studies Ofloxacin controlled release matrix tablets were prepared by wet granulation technique. In order to investigate the potential of Ethyl cellulose ether derivatives as a matrix material, Ofloxacin formulations with different types and grades of Ethocel were prepared at several drug-to-polymer ratios. The method adopted for in vitro drug release studies was USP Method-1 [rotating Basket Method] by Pharma test dissolution apparatus using phosphate buffer 7.4 pH as a dissolution medium. Various Kinetic models were employed to the formulations for the purpose of determination of release mechanism. A comparative study was performed between the tested Ofloxacin-Ethocel formulations and a standard reference obtained from the local market. FI dissimilarity factor and f2 similarity factor were applied to the formulations for the checking of dissimilarities and similarities between the tested formulations and reference standard

Preparation and evaluation of 5, 9-dimethyl-2-cyclopropyl-2-decanol as a penetration enhancer for drugs through rat skin

In the present study a new alcohol derivative of tetrahydrogeraniol [THG], an acyclic monoterpene, has been prepared by using Grignard reagent and methyl cyclopropyl ketone. Penetration enhancing effects of THG and the synthesized derivative 5,9-dimethyl-2-cyclopropyl-2-decanol [DICNOL] on the transdermal penetration of 5-fluorouracil [5-FU] and tramadol hydrochloride [tramadol HC1] across the excised rat skin were studied by an in vitro permeation technique using Franz diffusion cells. Azone was used as standard enhancer for comparison. DICNOL and THG significantly enhanced 5-FU and tramadol HC1 penetration through rat skin compared with the control. DICNOL enhanced the permeability of 5-FU and tramadol HC1 across full thickness skin by about 11 and 20 fold, respectively. Increased partition coefficient and diffusion coefficient values were obtained by these enhancers. The results suggest that the amount of DICNOL in the skin, especially in the stratum corneum, may be related to its penetration enhancing effects

Simultaneous analysis of the three hormones involved in spermatogenesis and their interrelation ratios

The Objectives of this non-interventional descriptive study was to determine the variation in serum levels of Luteinizing Hormone [LH], Follicle Stimulating Hormone [FSH] and Testosterone along with their ratios, among men having abnormal semen and their possible etiological role in male infertility. The study was carried out in the Reproductive Physiology Department of Public Health Laboratories Division, and National Institute of health [NIH], Islamabad during January 2004 to December 2005. Two hundred fifty married men who had presented with a complaint of infertility and who had an abnormal seminal profile on the basis of their prior semen analysis were included in the study. Subjects were classified as azoospermic [50], oligozoospermic [75], asthenozoospermic [50] and normozoospermic [75]. In addition [50] normal male subjects, who were known to have fathered children, were included as controls. LH, FSH and Testosterone levels were determined in serum by using Enzyme Immunoassay [EIA], using state-of-art Elecsys-2010 fully automatic Immunology analyzer by Roche Diagnostics [USA]. The FSH and LH level indicated inverse/negative correlation to sperm concentration in semen, while decreased Testosterone levels were associated with depleted sperm concentration. The findings indicate that not only the altered/disturbed concentrations of gonadotrophins and androgenic hormones are responsible for male sub-fertility but also the disturbances in gonadotrophic: androgenic hormones ratios lead to infertility since these all hormones act synergistically

In vitro antifungal activity of Rhazya stricta

Rhazya stricta is a small glabrous shrub, widely distributed throughout Western Asia from Yemen to Arabia, to the North West Province of India and abundantly found in various regions of Pakistan.Larvicidal and antifungal studies of polar and non polar aerial parts extracts of Rhazya stricta were performed using brine shrimps larvae for larvicidal study and for antifungal study microorganisms, Trichophyton longifusis, Aspergillus flavus, Candida albicans, Microsporum canis and Fusarium solani were used respectively. The methanol fraction showed significant cytotoxicity with LC[50] 17.809 micro g/ml, having mortality rate 73.33% at highest dose. While pet-ether, chloroform and carbon tetrachloride possessed moderate to low cytotoxicity with their LC[50] values 49.077 micro g/ml, 95.859 micro g/ml and 80.489 micro g/ml respectively, ethyl acetate fraction showed no cytotoxicity .Results of antifungal studies showed that fractionated samples of methanol and chloroform possessed significant antifungal activities against, Trichophyton longifusis, Aspergillusflavus, Candida albicans and Fusarium solani respectively. Due to these promising results, further in vivo studies over R. stricta must be conducted

influemce of different plasticizers on some physical and mechanical properties of hydroxypropyl methylcellulose free films

Coating has been widely used in pharmaceutical manufacture either as non-functional or a functional entity. The objectives of the present study were to investigate the effect of plasticizers such as PEG400, PEG1000 and triacetin on mechanical properties, glass transition temperature and water vapor transmission of free films prepared from HPMC and/or HPMC:PVA blends, to develop suitable coating system for tablets, and to determine the release profiles of the coated tablets. The tensile strength of plasticized HPMC films was generally lower than that of control HPMC film and could be attributed to increased crystallinity and segmental chain mobility of HPMC. This effect increased as the concentration of plasticizer increased. Generally the addition of both grades of polyethylene glycol [PEG400 and PEG1000] increased the moisture permeability of HPMC films but the films containing triacetin provided a more rigid barrier to moisture compared to unplasticized HPMC films. The dissolution profiles of paracetamol tablets coated with 7% w/v HPMC coating-solutions containing PEG400, PEG1000 and triacetin, and those containing PEG400 and PVA together showed that HPMC had weak water resistance. The presence of PEG400 and 1000 in HPMC films further weakened its resistance to solubility while the presence of triacetin caused a little increase in HPMC water resistance. From the results it was concluded that HPMC at 7%w/w concentration was suitable for film-coating intended for non-functional coating. Presence of the PEG 400, PEG1000 and triacetin as well as the presence of PVA and PEG400 together improved the coating properties of HPMC films and made it more suitable as a non-functional coating material