Solid lipid nanoparticles are at the forefront of the rapidly developing field of nanotechnology with several potential applications in drug delivery, clinical medicine and research, as well as in other varied sciences. Due to their unique size-dependent properties, lipid nanoparticles offer the possibility to develop new therapeutics. The ability to incorporate drugs into nanocarriers offers a new prototype in drug delivery that could be used for secondary and tertiary levels of drug targeting. Hence, solid lipid nanoparticles hold great promise for reaching the goal of controlled and site specific drug delivery and hence have attracted wide attention of researchers. This review presents a broad treatment of solid lipid nanoparticles discussing their advantages, limitations and their possible remedies. The different types of nanocarriers which were based on solid lipid like solid lipid nanoparticles, nanostructured lipid carriers, lipid drug conjugates are discussed with their structural differences. Different production methods which are suitable for large scale production and applications of solid lipid nanoparticles are described. Appropriate analytical techniques for characterization of solid lipid nanoparticles like photon correlation spectroscopy, scanning electron microscopy, differential scanning calorimetry are highlighted. Aspects of solid lipid nanoparticles route of administration and their biodistribution are also incorporated. If appropriately investigated, solid lipid nanoparticles may open new vistas in therapy of complex diseases.

Crystal form can be crucial to the performance of a dosage form. This is especially true for compounds that have intrinsic barriers to drug delivery, such as low aqueous solubility, slow dissolution in gastrointestinal media, low permeability and first-pass metabolism. The nature of the physical form and formulation tends to exhibit the greatest effect on bioavailability parameters of water insoluble compounds that need to be given orally in high doses. An alternative approach available for the enhancement of drug solubility, dissolution and bioavailability is through the application of crystal engineering of co-crystals. The physicochemical properties of the active pharmaceutical ingredients and the bulk material properties can be modified, whilst maintaining the intrinsic activity of the drug molecule. This article covers the advantages of co-crystals over salts, solvates (hydrates), solid dispersions and polymorphs, mechanism of formation of co-crystals, methods of preparation of co-crystals and application of co-crystals to modify physicochemical characteristics of active pharmaceutical ingredients along with the case studies. The intellectual property implications of creating co-crystals are also highly relevant.

Chitosan is a biocompatible, biodegradable and non-toxic polysaccharide polymer. It dissolves in water only if the pH is lower than 6.5. To extend its range of application, many water-soluble derivatives have therefore been prepared. In this research, chitosan-vitamin C complex was synthesized and characterized with Fourier transformed infrared spectroscopy, differential scanning calorimetry and ¹ H-NMR. The solubility of chitosan-vitamin C complex in distilled water was greatly improved. The •O₂ ^- scavenging activity of chitosan-vitamin C complex was compared with chitosan and vitamin C by measuring the auto-oxidation rate of pyrogallic acid. Results showed that the scavenging activity on •O₂ ^- by chitosan-vitamin C complex was stronger than that by CS. At low concentrations (<0.05 mg/ml), the scavenging activity of chitosan-vitamin C complex was stronger than that of vitamin C, but after certain concentrations (>0.1mg/ml), its scavenging activity was lower than that of vitamin C.

The use of local antibiotics from a biodegradable implant for chronic osteomyelitis is an attractive alternative. The implant delivers high antibiotic concentration at tissue levels, obliterates dead space, aids bone repair and does not need to be removed. The purpose of this paper is to develop and evaluate a calcium sulphate and polycaprolactone based composite biodegradable implantable delivery system of cefoperazone sodium. Implants were prepared by modified fabrication technique to avoid solvent use. Interaction studies were carried out to check any incompatibility between ingredients. Prepared implants were evaluated for various in vitro parameters like dimensions, hardness, tensile strength, drug release profile and sterility. Morphological changes in pellet before and after drug release were evaluated by scanning electron microscopy. The pellet were also tested for microbiological efficacy and compared with plain drug solution in different concentrations. Developed pellets are regular in shape and size with good tensile strength. The release profile displayed drug levels above MIC continuously up to 2 months. Wide zone of inhibition by pellet against Staph. aureus as compared to drug solution proves its efficacy in treatment of osteomyelitis.

A sensitive, rapid, reverse phase HPLC method is reported for analysis of Triphala Curna using gallic acid, chebulagic acid and chebulinic acid as markers. Validation data for the method has been provided. Unlike methods of recovery testing adopted for synthetic chemicals, a modified approach has been presented here for a formulation like Triphala Curna having three myrobalans in its composition. Data has been provided to demonstrate applicability of the method developed to assess the variation in the Triphala Curna preparations.

The aim of the current study was to design sustained release matrix tablets of venlafaxine hydrochloride using ion exchange resin with the incorporation of hydrophilic and hydrophobic polymer combinations. Venlafaxine HCl was loaded onto Indion 244 by batch method and then resinate were wet granulated with ethyl cellulose and blended with hydroxypropylmethylcellulose and compressed. A central composite design for 2 factors at 3 levels each was employed to systematically optimize drug release profile at 2 h and at 18 h. Hydroxypropylmethylcellulose and ethylcellulose were taken as the independent variables. Response surface plots and contour plots were drawn, and optimum formulations were selected by feasibility and grid searches. Resinate shows inadequate sustained release profile. Compressed matrices exhibited the anomalous release mechanism, as the value of release rate exponent (n) varied between 08109 and 08719, resulting in regulated and complete release until 20 h. Validation of optimization study, performed using five confirmatory runs, indicated very high degree of prognostic ability of response surface methodology, with mean percentage error as 1.152±1.88%. Regulated drug release study indicates that the hydrophilic and hydrophobic matrix tablets of venlafaxine resinate prepared using hydroxypropylmethylcellulose and ethylcellulose, can successfully be employed as a once-a-day oral controlled release drug delivery system.

In the present study stability of various known solvates of quinapril hydrochloride has been compared with nitromethane solvate. Nitromethane solvate was found to be more stable compared to other known solvates. Single crystal X-ray diffraction analysis of quinapril nitromethane solvate shows intermolecular hydrogen bonding between quinapril molecule and nitromethane. Stabilization of quinapril by forming strong hydrogen bonding network as in case of co-crystals was further studied by forming co-crystal with tris(hydroxymethyl)amino methane. Quinapril free base forms a stable salt with tris(hydroxymethyl)amino methane not reported earlier. Quinapril tris(hydroxymethyl)amino methane salt found to be stable even at 80° for 72 h i.e. hardly any formation of diketopiperazine and diacid impurity. As expected single crystal X-ray diffraction analysis reveals tris(hydroxymethyl)amino methane salt of quinapril shows complex hydrogen bonding network between the two entities along with ionic bond. The properties of this stable salt - stable in solid as well as solution phase, might lead to an alternate highly stable formulation.

Many plants used in Saurashtra folk medicine have been reported to exhibit high antibacterial and antioxidant activities. In the present study, some parts of five plants, Guazuma ulmifolia L., Manilkara zapota L., Melia azedarach L., Syzygium cumini L. and Wrightia tomentosa R.& S., were evaluated for their antibacterial activity, total phenol content, flavonoid content, 2,2-diphenyl-1-picrylhydrazyl free radical scavenging activity and phytochemical analysis, using successive extraction by cold percolation method with petroleum ether, ethyl acetate, methanol and water. In vitro antibacterial activity was evaluated against five bacterial strains viz. Bacillus subtilis, Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella typhimurium and Enterobacter aerogenes by agar well diffusion method. Among the plants screened, W. tomentosa leaf and fruit showed the best antibacterial activity. The Gram-positive bacteria were more susceptible than Gram-negative bacteria. Methanol extract of M. zapota showed the best 2,2-diphenyl-1-picrylhydrazyl free radical scavenging activity. Highest total phenol content was shown by M. zapota and S. cumini in methanol extract, while highest flavonoid content was shown by W. tomentosa stem in petroleum ether extract and ethyl acetate extract. In all the plants, cardiac glycosides and triterpenes were more as compared to other phytoconstituents.

The purpose of this study is to fabricate the polyethylene glycol matrix tablet by mold technique. Indomethacin and hydroxypropylmethylcellulose were used as model drug and polymer, respectively, in PEG matrix system. The physical and drug release characteristics of developed matrix tablet were studied. This inert carrier system comprising 7:3 polyethylene glycol 4000: polyethylene glycol 400 could effectively enhance the solubility of indomethacin and an addition of hydroxypropylmethylcellulose could sustain the drug release. Scanning electron microscope photomicrograph indicated the drug diffusion outward through the porous network of this developed matrix tablet into the dissolution fluid. Least square fitting the experimental dissolution data to the mathematical expressions (power law, first-order, Higuchi's and zero-order) indicated the drug release kinetics primarily as Fickian diffusion. Both the enhancement of drug dissolution and the prolongation of the drug release could be achieved for aqueous insoluble drug such as, indomethacin, by using polyethylene glycol-hydroxypropylmethylcellulose matrix system prepared with melting and mold technique.

Gel dosage forms are successfully used as drug delivery systems to control drug release and protect the medicaments from a hostile environment. The main objective is to formulate and evaluate in situ oral topical gels of clotrimazole based on the concept of pH triggered and ion activated systems. The system utilizes polymers that exhibit sol-to-gel phase transition due to change in specific physico-chemical parameters. A pH triggered system consisting of carbopol 934P (0.2-1.4% w/v) and ion triggered system using gellan gum (0.1-0.75% w/v) along with hydroxylpropylmethylcelluose E50LV was used to prolong the release of clotrimazole (0.1% w/v). Formulations were evaluated for gelling capacity, viscosity, gel strength, bioadhesive force, spreadability, microbiological studies and in vitro release. The use of carbopol as in situ gel forming system was substantiated by the property to transform into stiff gels when the pH was raised, whereas in gellan gum this transformation occurred in the presence of monovalent/divalent cations. Effect of calcium carbonate and other process parameters optimized and found that increase in calcium ions produced stronger gels. The drug content, clarity, and pH of the formulation were found to be satisfactory. The viscosity was found to be in the range 5 to 85 centipoise for the sol, whereas for the gels it was up to 16000 centipoise. The formulation showed pseudoplastic flow with thixotrophy. The maximum gel strength (using texture analyzer) and bioadhesion was found to be up to 6.5 g and 4 g, respectively. The optimized formulations were able to release the drug up to 6 h. The formulation containing gellan gum showed better sustained release compared to carbopol based gels.

In the present study, a novel series of 4-(2-aminophenyl)morpholines were synthesized and characterized by IR, ¹ H-NMR, ¹³ C NMR and mass spectral analysis. The synthesized compounds were screened for analgesic (100 and 200 mg/kg), antiinflammatory (200 and 400 mg/kg), antibacterial (Bacillus subtilis, Bacillus cereus, Staphylococcus epidermidis, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia coli) and antifungal (Candida albicans and Aspergillus niger) activities. The minimum inhibitory concentrations of the compounds were also ascertained by agar streak dilution method. N-benzylidine-2-morpholoino benzenamine (1) and N-(3-nitro benzylidine)-2-morpholino benzenamine (3) exhibited significant analgesic, antiinflammatory and antimicrobial activities.

A series of novel N-Sulphonamidomethyl piperzinyl fluoroquinolones were synthesized and screened antiviral activity. Eight compounds were synthesized through modifying the N ⁴ -hydrogen of piperazine in fluoroquinolones with formaldehyde and sulphanomides by Mannich reactions. The structures of the synthesized compounds were characterized by means of their IR and ¹ H-NMR spectral data. Synthesized compounds were screened for antiviral activity against influenza A (H1N1, H3N2, H5N1) and influenza B viruses in MDCK cell culture. The antiHIV activities of the new compounds were screened for antiviral activity against replication of HIV-1(III _B ) in MT-4 cells. Cytotoxicity of the synthesized compounds was also tested in mock-infected MDCK and MT-4 cells. Compound CF-SD and CF-SDM inhibits the influenza A (H1N1) and compound GF-SDM inhibit the replication of influenza A (H5N1) and B in MDCK cells. All compounds displayed cytostatic propertity in MT-4 cells. Among the compounds tested, GF-SDM (CC ₅₀ =39.44 ΅M) most toxic compound in this series.

In the present study the ethanol extract of the aerial part of Andrographis paniculata was prepared and evaluated for antimicrobial activity against eleven bacterial strains by determining minimum inhibitory concentration and zone of inhibition. Minimum inhibitory concentration values were compared with control and zone of inhibition values were compared with standard ciprofloxacin in concentration 100 and 200 μg/ml. The results revealed that, the ethanol extract is potent in inhibiting bacterial growth of both Gram-negative and Gram positive bacteria.

The degradation behavior of cefixime trihydrate was investigated under different stress conditions of acidic hydrolysis, alkaline hydrolysis and oxidation using spectrophotometry. Stability indicating spectrophotometric methods were developed that could separate the drug from its degradation products formed under these stress conditions. The UV spectral characteristics of the drug and degraded products were quite different and zero and first order derivative ultraviolet spectrophotometric methods were used to study the extent of degradation. Cefixime trihydrate was found to degrade extensively under experimental conditions. The methods were validated by establishing the linearity, inter and intraday precision, accuracy, selectivity and specificity.

Amukkarac curanam a polyherbal Siddha formulation was examined for its analgesic and antiinflammatory activity at a dose of 500 mg/kg, p.o. The experimental methods used were tail immersion and acetic acid induced writhing method for analgesic and cotton pellet induced granuloma formation for antiinflammatory activity. Pentazocine (10 mg/kg, intraperitoneally) and aspirin (150 mg/kg, orally) clinically used analgesics were used as standard analgesics. Indomethacin (10 mg/kg, orally) was used as standard for antiinflammatory study. Amukkarac curanam showed significant analgesic and antiinflammatory activity in the above study.

Shade dried, powdered seeds of Sterculia guttata were extracted using a Soxhlet extractor with ethanol. Ethanol was removed under reduced pressure and dried to obtained crude extract. This extract was evaluated for its effect on behavioral changes, exploratory activity and barbiturate-sleeping time, using appropriate standard methods in mice. The extract exhibited dose-dependent CNS depressant activity.

In the present work, fast disintegrating tablets of prochlorperazine maleate were designed with a view to enhance patient compliance by effervescent method. In this method, mixtures of sodium bicarbonate and anhydrous citric acid in different ratios along with crospovidone (2-10% w/w), croscarmellose sodium (2-10% w/w) were used as superdisintegrants. Estimation of prochlorperazine maleate in the prepared tablet formulations was carried out by extracting the drug with methanol and measuring the absorbance at 254.5 nm. The prepared formulations were further evaluated for hardness, friability, drug content uniformity and in vitro dispersion time. Based on in vitro dispersion time (approximately 13-21 s), two promising formulations (one from each super-disintegrant) were tested for in vitro drug release pattern in pH 6.8 phosphate buffer, short-term stability (at 40Ί/75% relative humidity for 3 mo) and drug-excipient interaction (IR spectroscopy). Among the two promising formulations, the formulation containing 10% w/w of crospovidone and mixture of 20% w/w sodium bicarbonate and 15% w/w of citric acid emerged as the overall best formulation (t _50% 6 min) based on drug release characteristics in pH 6.8 phosphate buffer compared to commercial conventional tablet formulation (t _50% 17.4 min). Short-term stability studies on the promising formulations indicated that there are no significant changes in drug content and in vitro dispersion time (p<0.05).

A simple, precise, accurate and rapid high performance thin layer chromatographic method has been developed and validated for the determination of clotrimazole in bulk drug and tablet dosage form. The stationary phase used was precoated silica gel 60F ₂₅₄ . The mobile phase used was a mixture of cyclohexane:toluene:methanol:triethyleamine (8:2:0.5:0.2 v/v/v/v). The detection of spot was carried out at 262 nm. The method was validated in terms of linearity, accuracy, precision and specificity. The calibration curve was found to be linear between 200 to 1000 ng/spot for clotrimazole. The limit of detection and the limit of quantification for clotrimazole were found to be 50 ng/spot and 200 ng/spot, respectively. The proposed method can be successfully used to determine the drug content of bulk drug and marketed formulation of tablet.

In the present study, antiinflammatory activity of the Piper longum dried fruit's oil was studied in rats using the carrageenan-induced right hind paw edema method. The activity was compared with that of standard drug ibuprofen. The dried fruit's oil inhibited carrageenan-induced rat paw edema. The results indicated that the dried fruit's oil produced significant (p< 0.001) antiinflammatory activity when compared with the standard and untreated control.

Dapsone has been the principal drug in a multidrug regimen recommended by the World Health Organization for the treatment of leprosy. It is also widely used by dermatologists in varied skin conditions like dermatitis herpetiformis, bullous pemphigoid, Behcet's disease, lupus erythematous and a host of other skin diseases. Hence an attempt has been made to review the utilization and qualitative evaluation of dapsone over a period of 6 months in a tertiary care teaching hospital. The study consisted of 80 patients (54 leprosy and 26 non-leprosy patients), prescribed with dapsone 100 mg oral once daily. The prescribing patterns of dapsone in leprosy and other dermatological conditions (non-leprosy) were analyzed and the safety, efficacy and appropriateness of the doses prescribed were reviewed. The adverse drug reactions observed in the study population were type I Lepra reactions, gastrointestinal side effects (abdominal pain and anorexia), peripheral neuropathy, other nervous side effects (insomnia, headache and vertigo) and other adverse reactions (fever and tinnitus). Patient information leaflets were distributed to patients to educate on the appropriate use of dapsone.

The study was designed to investigate analgesic and antipyretic activities of petroleum ether and alcohol extracts of Centratherum anthelminticum (L) Kuntze (family: Asteraceae) seeds (100 and 200 mg/kg, p.o.) in brewer's yeast-induced fever model in rats, acetic acid-induced writhing and Eddy's hot plate methods in mice. Both petroleum ether and alcohol extracts showed significant decrease in number of writhes in acetic acid-induced writhing and increase in paw licking time to heat stimuli in the hot plate method. The maximum analgesic activity was observed at 90 min after dosing when compared to control. Both the extracts showed significant inhibition of elevated body temperature when compared to corresponding control. These results suggested that the petroleum ether and alcohol extracts possessed analgesic and antipyretic activities.

Mebeverine hydrochloride is known to suffer from extensive first pass effect. In an attempt to improve its oral bioavailability and possibility to restrict its absorption only to the colon, mebeverine microspheres were prepared by emulsion solvent evaporation method. Four formulations were prepared with varying drug and polymer ratio. These formulations were subjected to various evaluation parameters like percent practical yield, entrapment efficiency, particle size, in vitro drug release, in vivo activity. Practical yield of the microspheres was up to 89.59% with encapsulation efficiency up to 79.4%. Scanning electron microscopy confirmed that the microsphere structures were smooth, spherical, and discrete and the particles were of the size range 200 to 300 ΅m. In vitro release of the drug showed biphasic release pattern with non-Fickian diffusion release in 12 h. On the basis of drug content, particle size, in vitro release and in vivo studies, formulation F-3 was found to be optimal. Antiirritable bowel syndrome activity was performed in colorectal distention in rat, which is a model for constipation-induced irritable bowel syndrome. The formulations F-2 and F-3 showed significant effect in fecal output when compared to the control as well as the marketed preparation in the constipation-induced irritable bowel syndrome in rats.

A binary mixture of imipramine HCl and chlordiazepoxide was determined by three different spectrophotometric methods. The first method involved determination of imipramine HCl and chlordiazepoxide using the simultaneous equations and the second method involved absorbance ratio method. Imipramine has absorbance maxima at 251 nm, chlordiazepoxide has absorbance maxima at 264.5 nm and isoabsorptive point is at 220 nm in methanol. Linearity was obtained in the concentration ranges of 1-25 and 1-10 μg/ml for Imipramine HCL and Chlordiazepoxide, respectively. The third method involved determination of these two drugs using the first-derivative spectrophotometric technique at 219 and 231.5 nm over the concentration ranges of 1-20 and 2-24 μg/ml with mean accuracies 99.46±0.78 and 101.43±1.20%, respectively. These methods were successively applied to pharmaceutical formulations because no interferences from the tablet excipients were found. The suitability of these methods for the quantitative determination of the compounds was proved by validation.

A binary mixture of amitriptyline HCl and chlordiazepoxide was determined by three different methods. The first method involved determination of amitriptyline HCl and chlordiazepoxide using the first derivative spectrophotometric technique at 219 and 230 nm over the concentration ranges of 1-20 and 2-24 μg/ml with mean accuracies 100.9±0.87 and 99.2±1.0%, respectively. The second method was reversed-phase high performance liquid chromatography using methanol: acetonitrile: 0.065 M ammonium acetate buffer (50:20:30, v/v/v), final pH adjust to 5.5 ± 0.02 with ortho phosphoric acid as the mobile phase and was pumped at a flow rate of 1.0 ml/min. Quantification was achieved with ultraviolet detection at 240 nm over concentration ranges of 0.25-4 and 0.1-1.6 μg/ml; mean accuracies were 100.55±0.62 and 100.71±0.81%, respectively. The third method utilized high performance thin layer chromatography method in tablet dosage form. The method was based on separation of the two drugs followed by densitometric measurements of their spots at 240 nm. The separation was carried out on Merck thin layer chromatographic aluminium sheets of silica gel 60 F254 using carbon tetrachloride: acetone: triethylamine (6:3:0.2, v/v/v) as mobile phase. The linearity was found to be in the range of 50-600 and 20-240 ng/spot for amitriptyline hydrochloride and chlordiazepoxide, respectively. The methods were successively applied to pharmaceutical formulation because no chromatographic interferences from the tablet excipients were found. The suitability of these methods for the quantitative determination of the compounds was proved by validation.

A binary mixture of fluoxetine HCl and olanzapine was determined by two different methods. The first method involved determination of fluoxetine HCl and olanzapine using reversed-phase liquid chromatography using acetonitrile:methanol:0.032 M ammonium acetate buffer (45:05:50, v/v/v) as the mobile phase at a flow rate of 1.5 ml/min. Quantitation was achieved with ultraviolet detection at 235 nm over concentration ranges of 0.2-4 and 0.1-2 μg/ml; mean accuracies were 101.16±0.59 and 99.79±0.56% for fluoxetine HCL and olanzapine, respectively. The second method was based on the high performance thin layer chromatography separation of the two drugs followed by densitometric measurements of their spots at 235 nm. The separation was carried out on Merck TLC aluminium sheets of silica gel 60 F254 using acetone:methanol:triethyleamine (5:3:0.5, v/v/v), as mobile phase. The linearity was found to be in the range of 300-1000 and 150-500 ng/spot; mean accuracies were 100.95±0.52 and 99.31±0.51% for fluoxetine HCl and olanzapine, respectively. The method was successively applied to tablets because no chromatographic interferences from the tablet excipients were found. The methods retained their accuracy and precision when the standard addition technique was applied. The results obtained by applying the proposed methods were statistically analyzed.