Formulation and bioequivalence of two valsartan tablets after a single oral administration

The aim of this study is to assess the quality of Valzan^® tablet (160 mg, valsartan immediate release test formulation) by comparing its pharmacokinetic parameters with Diovan^® tablet (160 mg, valsartan reference formulation). Valzan^® tablets were prepared according to a dry granulation method (roll compaction). To assess the bioequivalence of Valzan^® tablets a randomized, two-way, crossover, bioequivalence study was performed in 24 healthy male volunteers. The selected volunteers were divided into two groups of 12 subjects. One group was treated with the reference formulation (Diovan^®) and the other one with the generic Valzan^®, with a cross-over after the drug washout period of 14 days. Blood samples were collected at fixed time intervals and valsartan concentrations were determined by a validated HPLC assay method. The pharmacokinetic parameters AUC_0–48, AUC_0–∞, C_max, T_max, K_e and T_1/2 were determined for both the tablets and were compared statistically to evaluate the bioequivalence between the two brands of valsartan, using the statistical model recommended by the FDA. The analysis of variance (ANOVA) did not show any significant difference between the two formulations and 90% confidence intervals (CI) fell within the acceptable range for bioequivalence. Based on this statistical evaluation it was concluded that the test tablets (Valzan^®) is well formulated, since it exhibits pharmacokinetic profile comparable to the reference brand Diovan^®.     

Characterization of SNARE cleavage products generated by formulated botulinum neurotoxin type-a drug products

The study evaluated substrate cleavage product(s) generated by three botulinum neurotoxin serotype A (BoNT/A) medicinal drug products utilizing a novel and highly specific, light-chain activity, high-performance liquid chromatography (LCA-HPLC) method. Samples were reacted with a commercially available BoNT/A fluorescent substrate derived from the SNAP-25 sequence. Reaction products were separated by reversed-phase HPLC. The method detected an atypical cleavage pattern by one of the formulated drug products. IncobotulinumtoxinA produced two cleavage fragments rather than the single fragment typically generated by BoNT/A. Identification confirmed the secondary cleavage at a position corresponding to SNAP-25 Arg198-Ala199 (normal BoNT/A cleavage is Gln197-Arg198). Arg198-Ala199 is also the cleavage site for trypsin and serotype C toxin. Normal cleavage was observed for all other BoNT/A drug product samples, as well as 900-kD and 150-kD bulk toxin BoNT/A. The reason for this unexpected secondary cleavage pattern by one formulated BoNT/A drug product is unknown. Possible explanations include a contaminating protease and/or damage to the 150-kD type-A toxin causing nonspecific substrate recognition and subsequent cleavage uncharacteristic of type-A toxin. The BoNT/A drug products were also analyzed via the LCA-HPLC assay using a commercial BoNT/C fluorescent substrate derived from the syntaxin sequence. Cleavage of the serotype C substrate by incobotulinumtoxinA was also confirmed whilst neither of the other drug products cleaved the syntaxin substrate.     

Antiinflammatory, Analgesic and Antipyretic Activities of Mimusops elengi Linn

In the present study, 70% ethanol extract of Mimusops elengi Linn. bark was assessed for antiinflammatory, analgesic and antipyretic activities in animals. The antiinflammatory activity of ethanol extract of Mimusops elengi (200 mg/kg, p.o) was evaluated using carrageenan-induced paw edema and cotton pellet-induced granuloma models. Analgesic effect was evaluated using acetic acid-induced writhing and Eddy's hot plate models and antipyretic activity was assessed by Brewer's yeast-induced pyrexia in rats. The ethanol extract of Mimusops elengi (200 mg/kg, p.o) significantly inhibited the carrageenan-induced paw oedema at 3rd and 4th h and in cotton pellet model it reduced the transudative weight and little extent of granuloma weight. In analgesic models the ethanol extract of Mimusops elengi decreases the acetic acid-induced writhing and it also reduces the rectal temperature in Brewer's yeast induced pyrexia. However, Mimusops elengi did not increase the latency time in the hot plate test. These results show that ethanol extract of Mimusops elengi has an antiinflammatory, analgesic and antipyretic activity.     

Anti-inflammatory activity of Justicia prostrata gamble in acute and sub-acute models of inflammation

In this study, the aqueous (AQJP) and alcoholic (ALJP) extracts of the whole plant of Justicia prostrata Gamble (Acanthaceae) were screened for their acute and subacute anti-inflammatory activities using carrageenan-induced acute inflammation and cotton-pellet-induced granuloma (subacute inflammation), respectively, in rats. In the carrageenan-induced rat paw oedema model, both extracts were found to exhibit maximum reduction in paw volume at the first hour in a dose-dependent manner. At the dose of 500 mg/kg p.o., both extracts AQJP and ALJP showed maximum inhibition (51.39% and 62.5%, respectively) in rat paw oedema volume at the first hour of carrageenan-induced acute inflammation. In the cotton pellet granuloma assay, AQJP and ALJP at the dose of 500 mg/kg p.o. suppressed the transudative, exudative and proliferative phases of chronic inflammation. These extracts were able to (i) reduce the lipid peroxide content of exudates and liver and (ii) normalize the increased activity of acid and alkaline phosphatases in serum and liver of cotton pellet granulomatous rats. Preliminary phytochemical screening revealed the presence of lignans, triterpenes and phenolic compounds in ALJP, whereas phenolic compounds and glycosides in AQJP. The anti-inflammatory properties of these extracts may possibly be due to the presence of phenolic compounds. The anti-inflammatory effects produced by the extracts at the dose of 500 mg/kg, p.o. was comparable with the reference drug diclofenac sodium (5 mg/kg p.o.).     

Formulation and Evaluation of Pharmaceutically Equivalent Parenteral Depot Suspension of Methyl Prednisolone Acetate

The aim of the present study was to formulate and evaluate pharmaceutically equivalent injectable aqueous suspension for parenteral depot of methyl prednisolone acetate. Various aqueous suspensions were prepared by rapid stirring and colloid milling method. The prepared aqueous suspensions were subjected to particle size determination, sedimentation study, in vitro release studies (pH dependent dissolution study), and stability studies. The optimized formulation consisted of 4% w/w of methyl prednisolone acetate, 2.91% w/w of PEG-3350, 0.19% w/v of injection grade Tween-80, 0.68% w/w of monobasic sodium phosphate, 0.15% w/w of di-basic sodium phosphate, 0.91% w/v of benzyl alcohol, 0.32% w/w sodium meta bisulphate. The f₂ value was calculated for innovator (DepoMedrol^®, Batch No. MPH-0254) and optimized formulation at pH 6.8 and pH 7.4 phosphate buffers. The f₂ values of 62.94 and 54.37 were obtained at pH 6.8 and pH 7.4 phosphate buffers respectively. The particle size ranged 23-27 μm at D value of 0.9 for both test and innovator product.     

Effect of Flow Aids on Mucoadhesive Properties of Polymeric Discs of Polyoxyethylene and Carbopol 971P

The aim of present study is to investigate the effect of flow aids on the observed in vitro mucoadhesion of two representative polymers; polyoxyethylene and Carbopol^® 971P. More recently it has been shown that the addition of small amounts of certain excipients to a mucoadhesive formulation can lead to a substantial decrease in observed mucoadhesion in an in vitro test system, which suggests that formulation of these systems could be crucial in developing successful dosage forms. A series of experiments has been carried out which indicates that the presence of flow aids at high concentrations present in tablets can affect the observed ex-vivo mucoadhesive bond. Magnesium stearate (5%) exerts its negative effect on the mucoadhesion of Carbopol^® 971P and polyoxyethylene combination by hindering the hydration of the polymer. Adhesion time of formulation containing 5% magnesium stearate was found 4.7±0.34 h and percent hydration of same formulation was 70.12%.Talc and colloidal silicon dioxide (Aerosil), which do not possess the same hydrophobic properties or have available divalent cations were found to be viable alternatives to magnesium stearate.     

Recent Challenges in Insulin Delivery Systems: A Review

Relatively, a large percentage of world population is affected by diabetes mellitus, out of which approximately 5-10% with type 1 diabetes while the remaining 90% with type 2. Insulin administration is essential for type 1 patients while it is required at later stage by the patients of type 2. Current insulin delivery systems are available as transdermal injections which may be considered as invasive. Several non-invasive approaches for insulin delivery are being pursued by pharmaceutical companies to reduce the pain, and hypoglycemic incidences associated with injections in order to improve patient compliance. While any new insulin delivery system requires health authorities'' approval, to provide long term safety profile and insuring patients'' acceptance. The inhalation delivery system Exubera^® has already become clinically available in the United States and Europe for patients with diabetes as non-invasive delivery system.     

Response surface optimization of enzymatic hydrolysis and ROS scavenging activity of silk sericin hydrolysates

ContextSericin, a protein found in wastewater from the silk industry, was shown to contain a variety of biological activities, including antioxidant. The enzymatic conditions have been continuously modified to improve antioxidant effect and scavenging capacity against various free radicals of silk sericin protein.ObjectiveVariables in enzymatic reactions, including pH, temperature and enzyme/substrate ratio were analysed to discover the optimum conditions for antioxidant activity of sericin hydrolysates.Materials and methodsHydrolysis reaction catalysed by Alcalase^® was optimized through response surface methodology (RSM) in order to generate sericin hydrolysates possessing potency for % inhibition on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals, ferric-reducing power and peroxyl scavenging capacity. Flow cytometry was performed to evaluate cellular ROS level in human HaCaT keratinocytes and melanin-generating MNT1 cells pre-treated either with 20 mg/mL RSM-optimized sericin hydrolysates or 5 mM N-acetyl cysteine (NAC) for 60 min prior exposure with 1 mM hydrogen peroxide (H₂O₂).ResultsAmong these three variables, response surface plots demonstrate the major role of temperature on scavenging capacity of sericin hydrolysates. Sericin hydrolysates prepared by using Alcalase^® at RSM-optimized condition (enzyme/substrate ratio: 1.5, pH: 7.5, temperature: 70 °C) possessed % inhibition against H₂O₂ at 99.11 ± 0.54% and 73.25 ± 8.32% in HaCaT and MNT1 cells, respectively, while pre-treatment with NAC indicated the % inhibition only at 30.26 ± 7.62% in HaCaT and 51.05 ± 7.14% in MNT1 cells.Discussion and conclusionsThe acquired RSM information would be of benefit for further developing antioxidant peptide from diverse resources, especially the recycling of waste products from silk industry.     

Equilibrium and release properties of aqueous dispersions of non-steroidal anti-inflammatory drugs complexed with polyelectrolyte eudragit e 100

Equilibria and release properties of aqueous systems consisting of a set of five non-steroidal anti-inflammatory drugs (AH) complexed with the cationic polymethacrylate Eudragit E 100 (EU) are reported in this study. The composition (EU(AH)(50) (HCl)(50)) having fifty mole percent of each counterion (A(-) and Cl(-)) produces clear, stable aqueous dispersions in which a remarkably high proportion of AH (higher than 98%) is condensed with the PE under the form of ion pairs. This property expands the interval of pH in which AH are aqueous soluble. The set of AH contains members with and without an alpha methyl group (-(CH(3))CH-COOH: Flurbiprofen, Naproxen, Ketoprofen) and (-CH(2)-COOH: Diclofenac, Indomethacin). The proportion of ion pairs in the complexes was lower in the former group. Release of AH from the complexes toward a saline (NaCl 0.9%) solution was assayed in Franz cells. The five complexes behaved as drug carriers that exhibited a slow drug release with a remarkable zero order. In line with the percentages of counterionic condensation observed, release rates from -(CH(3))CH-COOH complexes were clearly higher than those of -CH(2)-COOH ones.     

Antiinflammatory Activity of Aqueous Extract of Stereospermum kunthianum (Cham, Sandrine Petit) Stem Bark in Rats

Stereospermum kunthianum, Cham, Sandrine Petit (family: Bignoniaceae) is used in traditional medicine to treat bronchitis, pneumonia and coughs, gastritis, wounds, rheumatic arthritis, ulcers, dysentery, leprosy and venereal diseases in humans. The antiinflammatory activity of the aqueous extract of the stem bark was investigated with experimental animal models using the carrageenan-induced paw oedema, leucocytes migration and granuloma air pouch tests in rats. The extract (100, 200 or 400 mg/kg) at 3 h post-treatment caused a significant (p<0.05) reduction in the paw oedema in rats. The effect of the extract was most pronounced at the dose of 400 mg/kg and was higher than that of indomethacin (10 mg/kg). The extract (400 mg/kg) caused a significant (p<0.05) reduction in the number of recruited leucocytes and it''s inhibition of peritoneal exudate formation was comparable to that of indomethacin at a dose of 10 mg/kg. The exudate formation inhibited by 400 mg/kg of the extract in the granuloma air pouch test was comparatively less to that of indomethacin at a dose of 10 mg/kg. The findings of the study indicate that the aqueous extract of Stereospermum kunthianum stem bark possesses antiinflammatory activity which is probably related to the inhibition of prostaglandin synthesis. This is a possible rationale for its folkloric use as an antiinflammatory agent.     

Evaluation of clinical activity and safety of Daflon 500 mg in type 2 diabetic female patients

Background

The incidence of cardiovascular disease in patients with type 2 diabetes mellitus is approximately twice as high as in the non-diabetic population.

Aim

To investigate the hypoglycemic and hypocholesterolemic effects of Daflon^® 500 mg (DF) administration together with its tolerability and efficacy in reducing the cardiovascular metabolic risk factors in female patients with type 2 diabetes.

Methods

In a well-adequate controlled single-blinded randomized parallel design the tolerability and the efficacy of Daflon^® (500 mg) either alone or with oral hypoglycemic, twice daily for 45 days, was studied in 36 female patients with type 2 diabetes.

Results

None of the patients in the studied groups were reported to have any adverse events throughout the treatment period (45 days), liver and kidney function tests were within normal limits and there was no significant difference between the pre-treatment (day 0) and post-treatment (day 45) values. Female patients receiving Daflon^® either alone or with oral hypoglycemic showed significant decrease in serum glucose; fructosamine; total cholesterol; LDL–cholesterol; triglycerides; malondialdehydes (as index of lipid peroxidation) and C-reactive protein (CRB) levels along with increase in the levels of nitric oxide and blood glutathione.

Conclusion

This study has shown that Daflon^® (500 mg, twice daily for 45 days) is helpful in reducing glucose level and the risk of cardiovascular disease in type 2 diabetic patients.

Recommendation

Further clinical trials are essential for strengthening the evidence base on the role of this drug in the cardiovascular risk in diabetic patients.     

Evaluation of the anti-inflammatory activity of Aegle marmelos (Bilwa) root

Aims and objectives:

The purpose of this study was to evaluate and compare the anti-inflammatory activity of the aqueous root bark extract of Aegle marmelos (Bilwa) in experimental acute and chronic inflammatory animal models.

Materials and Methods:

Aqueous extract of root bark of Bilwa was prepared and tested for anti-inflammatory activity in albino rats weighing 150-280 grams. The animals were randomly divided into 3 groups of 6 each; one group served as control and other two groups received indomethacin and Bilwa orally 1 hour prior to experimentation. The in vivo anti-inflammatory activity was studied using the acute (Carrageenan induced paw edema) and chronic (Cotton pellet induced granuloma) animal models. Anti-inflammatory activity was expressed as Percent inhibition (PI). Statistical analysis was performed using One-way analysis of variance (ANOVA) followed by Scheffe''s post hoc test. P < 0.05 was considered statistically significant.

Results:

The PI with indomethacin and Bilwa in carrageenan induced paw edema were 52.7% and 46% and in cotton pellet induced granuloma were 24.7% and 9.2% respectively. Indomethacin showed highly significant anti-inflammatory activity in both the models. However, Bilwa showed highly significant activity in acute model and but a trend of anti-inflammatory activity in chronic model studied.

Conclusions:

As Bilwa showed significant anti-inflammatory activity in the models studied, it can be a promising anti-inflammatory agent.     

Formulation and evaluation of trimetazidine dihydrochloride extended release tablets by melt congealing method

Trimetazidine dihydrochloride, a cellular antiischemic agent indicated in the management and prophylaxis of angina pectoris is given as 20 mg thrice daily in the conventional dosage regimen. The purpose of the present study was to formulate and evaluate twice a day extended release tablets containing 30 mg trimetazidine dihydrochloride. The method developed to formulate these extended release tablets was melt congealing followed by wet granulation which exhibited uniform sustained release action and overcame the drawbacks of multidosing. The formulation was developed with Methocel^® K100M and stearic acid as release retardant.     

Ranitidine Hydrochloride-loaded Ethyl Cellulose and Eudragit RS 100 Buoyant Microspheres: Effect of pH Modifiers

A floating type of dosage form of ranitidine hydrochloride in the form of microspheres capable of floating on simulated gastric fluid was prepared by solvent evaporation technique. Microspheres prepared with ethyl cellulose, Eudragit^® RS100 alone or in combination were evaluated for percent yield, drug entrapment, percent buoyancy and drug release and the results demonstrated satisfactory performance. Microspheres exhibited ranitidine hydrochloride release influenced by changing ranitidine hydrochloride-polymer and ranitidine hydrochloride-polymer-polymer ratio. Incorporation of a pH modifier has been the usual strategy employed to enhance the dissolution rate of weakly basic drug from floating microspheres. Further citric acid, fumaric acid, tartaric acid were employed as pH modifiers. Microspheres prepared with ethyl cellulose, Eudragit^® RS100 and their combination that showed highest release were utilized to study the effect of pH modifiers on ranitidine hydrochloride release from microspheres which is mainly affected due to modulation of microenvironmental pH. In vitro release of ranitidine hydrochloride from microspheres into simulated gastric fluid at 37° showed no significant burst effect. However the amount of release increased with time and significantly enhanced by pH modifiers. 15% w/w concentration of fumaric acid provide significant drug release from ranitidine hydrochloride microspheres prepared with ranitidine hydrochloride:ethyl cellulose (1:3), ranitidine hydrochloride:Eudragit^® RS100 (1:2) and ranitidine hydrochloride:ethyl cellulose:Eudragit^® RS100 (1:2:1) whereas citric acid, tartaric acid showed significant cumulative release at 20% w/w. In all this study suggest that ethyl celluose, Eudragit^® RS100 alone or in combination with added pH modifiers can be useful in floating microspheres which can be proved beneficial to enhance the bioavailability of ranitidine hydrochloride.     

A Holy Grail of asthma management: toward understanding how long-acting beta(2)-adrenoceptor agonists enhance the clinical efficacy of inhaled corticosteroids

There is unequivocal evidence that the combination of an inhaled corticosteroid (ICS) -- i.e. glucocorticoid -- and an inhaled long-acting beta(2)-adrenoceptor agonist (LABA) is superior to each component administered as a monotherapy alone in the clinical management of asthma. Moreover, Calverley and colleagues (Lancet 2003, 361: 449-456; N Engl J Med 2007, 356: 775-789) reporting for the 'TRial of Inhaled STeroids ANd long-acting beta(2)-agonists (TRISTAN)' and 'TOwards a Revolution in COPD Health (TORCH)' international study groups also demonstrated the superior efficacy of LABA/ICS combination therapies over ICS alone in the clinical management of chronic obstructive pulmonary disease. This finding has been independently confirmed indicating that the therapeutic benefit of LABA/ICS combination therapies is not restricted to asthma and may be extended to other chronic inflammatory diseases of the airways. Despite the unquestionable benefit of LABA/ICS combination therapies, there is a vast gap in our understanding of how these two drugs given together deliver superior clinical efficacy. In this article, we review the history of LABA/ICS combination therapies and critically evaluate how these two classes of drugs might interact at the biochemical level to suppress pro-inflammatory responses. Understanding the molecular basis of this fundamental clinical observation is a Holy Grail of current respiratory diseases research as it could permit the rational exploitation of this effect with the development of new 'optimized' LABA/ICS combination therapies.     

Evaluation of Parmotrema reticulatum Taylor for Antibacterial and Antiinflammatory Activities

Lichens produce variety of secondary metabolites including depsides, depsidones and dibenzofurans having multifunctional activity in response to external environmental condition. Present study provides evidence for in vitro antibacterial and in vivo antiinflammatory activity of acetone and ethanol extracts of Parmotrema reticulatum. In vitro antibacterial activity was investigated against gram positive and gram negative bacteria. Cotton pellet-induced granuloma, xylene-induced ear swelling, carragennan-induced edema, histamine-induced and carboxymethylcellulose sodium-induced leukocyte emigration in mice models were used to quantify the antiinflammatory activity. Acetone and ethanol extracts were showed antibacterial activity against Bacillus subtilis (minimal inhibitory concentration: 100 and 150 μg/ml) and Staphylococcus aureus (minimal inhibitory concentration: 100 and 200 μg/ml), Escherichia coli (minimal inhibitory concentration: 200 and 250 μg/ml), and Pseudomonasa eruginosa (minimal inhibitory concentration: 200 and 300 μg/ml). Acetone extract was inhibited edema significantly at 200 mg/kg with xylene, cotton pellet, carragennan and histamine induced edema in vivo models. Ethanol extract was found effective at dose of 300 mg/kg with all in vivo antiinflammatory models. The results showed significant (P<0.01) antiinflammatory effects at 200 and 300 mg/kg dose of acetone and ethanol extracts, respectively, which can be concluded that significant activity may be due to presence of flavanoids in ethanol extract and usnic acid in acetone extract.     

Antiinflammatory Activity of Hot Water Infusion of Nyctanthes arbo-tristis Flowers

In Sri Lankan ethnomedicate it is claimed the flowers of Nyctanthes arbo-tristis is effective in the treatment of inflammatory conditions but this has not been scientifically validated. This experiment was carried to investigate the antinflammatory potential of hot water infusion of Nyctanthes arbo-tristis flowers. Oral antiinflammatory activity of hot water infusion of Nyctanthes arbo-tristis flowers (concentrations: 3.75, 7.5, 12.5 and 18.75 mg/kg) was assessed in rats using both acute (carrageenan-induced paw oedema assay) and chronic (formaldehyde induced-paw oedema and cotton pellet-granuloma tests) inflammatory models. In an attempt to investigate its mode of action, antihistamine activity (by wheal test), inhibition of prostaglandin synthesis (by enteropooling test), inhibition of Tumor necrosis factor_α secretion (using human mononuclear cells), and suppression of vascular permeability (acetic acid-induced vascular permeability test) and cytotoxicity (Evans blue test) were assessed. In the carrageenan-induced paw oedema test, hot water infusion simultaneously suppressed both initial and late stages of inflammation in an inversely dose related manner. Hot water infusion also inhibited paw oedema in formalin and cotton pellet granuloma tests. In addition, this infusion exhibited marked anti histamine activity, prostaglandin synthesis inhibition and suppression of vascular permeability. These findings scientifically support the traditional use of Nyctanthes arbo-tristis flowers in treatment of inflammatory conditions.     

Validation of a Stability-Indicating RP-HPLC Method for the Simultaneous Determination of Trimethoprim and Sulfadimethoxine Sodium in Oral Liquid Dosage Form

A simple, specific, accurate, and stability-indicating RP-HPLC method was developed and validated for the simultaneous determination of Trimethoprim (TMP) and Sulfadimethoxine sodium (SDMS) in Vetricine^® oral solution product. The desired separation was achieved on an ODS column (250×4.6 mm i.d., 5 μm) at room temperature. The optimized mobile phase consisted of an isocratic solvent mixture of water:acetonitrile:triethylamine (700:299:1, v/v/v), adjusted to a pH of 5.7 ± 0.05 with 0.2N acetic acid. The mobile phase was fixed at 0.8 ml/min and the analytes were monitored at 254 nm using a photodiode array detector. The effects of the chromatographic conditions on the peaks USP tailing factor, column efficiency, and resolution were systematically optimized. Forced degradation experiments were carried out by exposing TMP, SDMS standards, and the oral solution formulation to thermal, photolytic, oxidative, and acid-base hydrolytic stress conditions. The degradation products were well-resolved from the main peaks and the excipients, thus proving the reliable stability-indicating method. The method was validated as per ICH and USP guidelines (USP34/NF29) and found to be adequate for the routine quantitative estimation of TMP and SDMS in commercially available Vetricine® oral liquid dosage form.     

Screening of Alkaloidal Fraction of Conium maculatum L. Aerial Parts for Analgesic and Antiinflammatory Activity

Conium maculatum Linn. (Umbelliferae) has been traditionally used in the treatment of spasmodic disorders, and to relieve nervous excitation, rheumatic pains in the old and feeble, pain in stomach, pain of gastric ulcer, nervousness and restlessness. Alkaloids have long been considered as bioactive group of constituents present in C. maculatum. Despite a long tradition of use, C. maculatum has not been evaluated pharmacologically to validate its traditional claims for analgesic and antiinflammatory activities. Thus, the present investigations were undertaken with an objective to evaluate alkaloidal fraction of C. maculatum aerial parts for analgesic and antiinflammatory activities. Test doses (100 or 200 mg/kg, p.o.) of alkaloidal fraction were evaluated for analgesic activity using tail flick test and antiinflammatory activity using carrageenan-induced paw oedema test in rats. Morphine (5 mg/kg, p.o.) and indomethacin (5 mg/kg, p.o.) were used as standard analgesic and antiinflammatory drugs, respectively. Alkaloidal fraction of the plant exhibited significant analgesic activity at a dose of 200 mg/kg as it showed significant increase in tail flicking reaction time with respect to the control during 2 h intervals of observation. It also exhibited significant antiinflammatory activity at a dose of 200 mg/kg as it inhibited paw oedema in rats to 71% and reduced the paw volume one-fourth to the control during 1^st h of the study. The present investigations suggest that alkaloids are responsible for analgesic and antiinflammatory activities of C. maculatum.     

PLGA-modified Syloid®-based microparticles for the ocular delivery of terconazole: in-vitro and in-vivo investigations

The eye is an invulnerable organ with intrinsic anatomical and physiological barriers, hindering the development of a pioneer ocular formulation. The aim of this work was to develop an efficient ocular delivery system that can augment the ocular bioavailability of the antifungal drug, terconazole. Mesoporous silica microparticles, Syloid^® 244 FP were utilized as the carrier system for terconazole. Preliminary studies were carried out using different drug:Syloid^® weight ratios. The optimum weight ratio was mixed with various concentrations (30 and 60%w/w) of poly (lactic-co-glycolic acid) (PLGA), ester or acid-capped and with different monomers-ratio (50:50 and 75:25) using the nano-spray dryer. Results revealed the superiority of drug:Syloid^® weight ratio of 1:2 in terms of yield percentage (Y%), SPAN and drug content percentage (DC%). Furthermore, incorporation of PLGA with lower glycolic acid monomer-ratio significantly increased Y%. In contrast, increasing the glycolic acid monomer-ratio resulted in higher DC% and release efficiency percentage (RE%). Additionally, doubling PLGA concentration significantly reduced Y%, DC%, drug loading percentage (DL%) and RE%. Applying desirability function in terms of increasing DC%, DL% besides RE% and decreasing SPAN, the selected formulation was chosen for DSC, XRD and SEM investigations. Results confirmed the successful loading of amorphized terconazole on PLGA-modified Syloid^® microparticles. Moreover, pharmacokinetic studies for the chosen formulation on male Albino rabbits’ eyes revealed a 2, 6.7 and 25.3-fold increase in mean residence time, C_max and AUC_0–24-values, respectively, compared to the drug suspension. PLGA-modified Syloid^® microparticles represent a potential option to augment the bioavailability of ocular drugs.