Inderbir Singh

Tramadol-Induced Seizurogenic Effect: A Possible Role of Opioid-Dependent γ-Aminobutyric Acid Inhibitory Pathway

The present study has been designed to pharmacologically investigate the role of opioid and gamma-aminobutyric acid receptors on the seizurogenic effect of tramadol. A single injection of pentylenetetrazole (80 mg/kg) was used to elicit seizure activity in mice. Seizures were assessed in terms of the time latency of the onset of Straubs tail phenomenon, onset of jerky movements of whole body, convulsions and death. Tramadol administration (50 mg/kg) caused a marked increase in seizurogenic activity of pentylenetetrazole as measured in terms of a significant decrease in the time latency of the onset of Straubs tail phenomenon, jerky movements of whole body, convulsions and death. Moreover, prior administration of naloxone (2 mg/kg) and gabapentin (25 mg/kg), respectively, attenuated the seizurogenic activity that tramadol exerted on pentylenetetrazole-treated mice. Furthermore, prior administration of naloxone (2 mg/kg) and gabapentin (25 mg/kg), respectively, also attenuated the seizurogenic activity exerted by tramadol per se. Therefore, it is suggested that tramadol exerts a seizurogenic effect on mice possibly via an opioid-dependent gamma-aminobutyric acid inhibitory pathway.

Formulation and evaluation of controlled release matrix mucoadhesive tablets of domperidone using Salvia plebeian gum

The aim of study was to prepare controlled release matrix mucoadhesive tablets of domperidone using Salvia plebeian gum as natural polymer. Tablets were formulated by direct compression technology employing the natural polymer in different concentrations (5, 10, 15 and 20% w/w). The prepared batches were evaluated for drug assay, diameter, thickness, hardness and tensile strength, swelling index, mucoadhesive strength (using texture analyzer) and subjected to in vitro drug release studies. Real-time stability studies were also conducted on prepared batches. In vitro drug release data were fitted in various release kinetic models for studying the mechanism of drug release. Tensile strength was found to increase from 0.808 ± 0.098 to 1.527 ± 0.10 mN/cm2 and mucoadhesive strength increased from 13.673 ± 1.542 to 40.378 ± 2.345 N, with an increase in the polymer concentration from 5 to 20% (A1 to A4). Swelling index was reported to increase with both increase in the concentration of gum and the time duration. The in vitro drug release decreased from 97.76 to 83.4% (A1 to A4) with the increase in polymer concentration. The drug release from the matrix tablets was found to follow zero-order and Higuchi models, indicating the matrix-forming potential of natural polymer. The value of n was found to be between 0.5221 and 0.8992, indicating the involvement of more than one drug release mechanism from the formulation and possibly the combination of both diffusion and erosion. These research findings clearly indicate the potential of S. plebeian gum to be used as binder, release retardant and mucoadhesive natural material in tablet formulations.

Carbon Nanotubes: Synthesis, Properties and Pharmaceutical Applications

Carbon nanotubes (CNTs) are unique cylindrical forms of carbon that have carved a niche in the field of nanomedicine. The possibility of incorporating functionalized carbon nanotubes into cells and the biological milieu offers numerous advantages for potential applications in biology, pharmacology and drug delivery. One of the most promising is the utilization of CNTs as a new carrier system for the delivery of therapeutic molecules. Furthermore, recent findings of improved cell membrane permeability for carbon nanotubes would expand medical applications to therapeutics using carbon nanotubes as carriers in gene delivery systems. This review discusses the synthetic methods, properties and potential pharmaceutical application of CNTs. Toxicological considerations of CNTs have also been delineated.

Taste masked microspheres of ofloxacin: formulation and evaluation of orodispersible tablets.

Ofloxacin is a synthetic chemotherapeutic antibiotic used for treatment of a variety of bacterial infections, but therapy suffers from low patients’ compliance due to its unpleasant taste. This study was aimed to develop taste masked microspheres of ofloxacin using Eudragit and to prepare orodispersible tablets of the formulated microspheres using natural superdisintegrant. Taste masking Eudragit E100 microspheres were prepared by solvent evaporation technique with an entrapment efficiency ranging from 69.54 ± 1.98 to 86.52 ± 2.25%. DSC revealed no interaction between the drug and polymer. Microspheres prepared at a drug/polymer ratio of 1:4 and 1:5 revealed sufficient flow properties and better taste masking as compared to other ratios. Drug loaded microspheres were formulated as orodispersible tablets using locust bean gum as a natural superdisintegrant offering the advatages of biocompatibility and biodegrad-ability. The wetting time, water absorption ratio and in-vitro disintegration time of the tablets were found to range between 19 ± 2 to 10 ± 3 seconds, 59.11 ± 0.65 to 85.76 ± 0.96 and 22 ± 2 to 10 ± 2 seconds, respectively. The in-vitro ofloxacin release was about 97.25% within 2h. The results obtained from the study suggested the use of eudragit polymer for preparing ofloxacin loaded microspheres with an aim to mask the bitter taste of the drug and furthermore orodispersible tablets could be formulated using locust bean gum as a natural superdisintegrant.

Formulation and characterization of tramadol-loaded IPN microgels of alginate and gelatin: Optimization using response surface methodology.

Formulation and characterization of tramadol-loaded IPN microgels of alginate and gelatin: Optimization using response surface methodology Tramadol-loaded interpenetrating polymer network (IPN) alginate-gelatin (AG) microgels (MG) were prepared by the chemical cross-linking technique with glutaraldehyde as cross-linking agent and were optimized using response surfaces. A central composite design for 2 factors, at 3 levels each, was employed to evaluate the effect of critical formulation variables, namely the amount of gelatin (X1) and glutaraldehyde (X2), on geometric mean diameter, encapsulation efficiency, diffusion coefficient (D), amount of mucin adsorbed per unit mass (Qe) and 50 % drug release time (t50). Microgels with average particle size in the range of 44.31-102.41 μm were obtained. Drug encapsulation up to 86.5 % was achieved. MGs were characterized by FT-IR spectroscopy to assess formation of the IPN structure and differential scanning calorimetry (DSC) was performed to understand the nature of drug dispersion after encapsulation into IPN microgels. Both equilibrium and dynamic swelling studies were performed in pH 7.4 phosphate buffer. Diffusion coefficients and exponents for water transport were determined using an empirical equation. The mucoadhesive properties of MGs were evaluated in aqueous solution by measuring the mucin adsorbed on MGs. Adsorption isotherms were constructed and fitted with Freundlich and Langmuir equations. In vitro release studies indicated the dependence of drug release on the extent of cross-linking and the amount of gelatin used in preparing IPNs. The release rates were fitted to a power law equation and Higuchis model to compute the various drug transport parameters, n value ranged from 0.4055 to 0.5754, suggesting that release may vary from Fickian to quasi-Fickian depending upon variation in the formulation composition. Izrada i karakterizacija IPN alginatnih i želatinskih mikrogelova s tramadolom: Optimiranje pomoću metode odzivnih površina Interpenetrirajući umreženi polimerni (IPN) alginatno-želatinski (AG) mikrogelovi (MG) tramadola pripravljeni su metodom umrežavanja koristeći glutaraldehid kao sredstvo za umrežavanje. Pripravci su optimirani pomoću odzivnih površina. Kompozitini dizajn s dva faktora na tri nivoa upotrijebljen je za procjenu kritičnih formulacijskih varijabli: praćen je utjecaj količine želatine (X1) i glutaraldehida (X2) na prosječnu veličinu čestica, sposobnost kapsuliranja, koeficijent difuzije (D), količinu adsorbiranog mucina po jedinici mase (Qe) i vrijeme potrebno za oslobađanje 50 % lijeka (t50). Dobiveni su mikrogelovi prosječne veličine čestica od 44,31 do 102,41 ?m, a maksimalno postignuto vezanje lijeka bilo je 86,5 %. Mikrogelovi su karakterizirani FT-IR spektroskopijom i diferencijalnom pretražnom kalorimetrijom (DSC). Ravnotežne i dinamičke studije bubrenja provedene su u fosfatnom puferu pH 7,4. Koeficijenti difuzije i eksponenti za transport vode određeni su pomoću empirijske jednadžbe. Mukoadhezivna svojstva MGs evaluirana su u vodenoj otopini mjerenjem adsorpcije mucina na mikrogelove. Konstruirane su adsorpcijske izoterme i uspoređene s Freudlichovim i Langmuirovim jednadžbama. Pokusi in vitro pokazuju da oslobađanje ljekovite tvari ovisi o stupnju umreženja i količini želatine upotrijebljene u pripravi IPN. Vrijednosti oslobađanja uvrštene su u jednadžbu zakona potencije i u Higuchijev model kako bi se izračunali razni parametri prijenosa lijeka; n vrijednosti bile su između 0,4055 i 0,5754, što ukazuje na to da oslobađanje varira od Fickovog do kvazi-Fickovog, ovisno o sastavu pripravka.

Pharmaceutical Applications of Chemometric Techniques

Chemometrics involves application of various statistical methods for drawing vital information from various manufacturing-related processes. Multiway chemometric models like parallel factor analysis (PARAFAC), Tucker-3, N-partial least square (N-PLS), and bilinear models like principle component regression (PCR) and partial least squares (PLS) have been discussed in the paper. Chemometric approaches can be used to analyze the data obtained from various instruments including near infrared (NIR), attenuated total reflectance Fourier transform infrared (ATR-FTIR), high-performance liquid chromatography (HPLC), and terahertz pulse spectroscopy. The technique has been used in the quality assurance and quality control of pharmaceutical solid dosage forms. Moreover, application of chemometric methods in the evaluation of properties of pharmaceutical powders and tablet parametric tests has also been discussed in the review. It has been suggested as a useful method for the real-time in-process testing and is a valuable process analytical tool.

Design and Evaluation of Voriconazole Loaded Solid Lipid Nanoparticles for Ophthalmic Application.

Voriconazole is a second-generation antifungal agent with excellent broad spectrum of antifungal activity commercially available for oral and intravenous administration. Systemic administration of voriconazole is associated with side effects including visual and hepatic abnormalities. This study assessed the feasibility of using solid lipid nanoparticles for ocular delivery of voriconazole adopting stearic acid as lipidic material, tween 80 as a stabilizer, and Carbopol 934 as controlled release agent and for increasing the precorneal residence time in eye. The systems were prepared using two different methods, that is, ultrasonication method and microemulsion technique. The results indicated that the larger particle size of SLNs was found with microemulsion technique (308 ± 3.52 nm to 343 ± 3.51) compared to SLN prepared with ultrasonication method (234 ± 3.52 nm to 288 ± 4.58 nm). The polydispersity index values were less than 0.3 for all formulations and zeta potential of the prepared formulations by these two methods varied from −22.71 ± 0.63 mV to −28.86 ± 0.58 mV. Powder X-ray diffraction and differential scanning calorimetry indicated decrease in crystallinity of drug. The in vitro release study and the SLN formulations prepared with ultrasonication method demonstrated sustained release up to 12 hours. This study demonstrated that SLN prepared by ultrasonication method is more suitable than microemulsion technique without causing any significant effect on corneal hydration level.

Formulation and evaluation of transdermal composite films of chitosan-montmorillonite for the delivery of curcumin.

Composite transdermal films of chitosan (CS)/montmorillonite K 10 (MMT) clay were prepared for the delivery of curcumin. CS/MMT films were evaluated for various physicochemical parameters. The films were characterized by Fourier transform infrared spectroscopy and X-ray diffraction analysis. Water uptake and swelling ratio of the films was found to decrease with increase in concentration of clay. Mechanical properties of the films were assessed in terms of tensile strength and extensibility using texture analyzer. Increase in tensile strength and reduction in extensibility was reported with increase in the clay content. This was attributed to the formation of intercalated structure and restriction in mobility of CS polymeric chains with the inclusion of clay particles. In vitro drug release study on transdermal films indicated pronounced sustained release of curcumin by the incorporation of clay particles in the CS polymer matrix. Stability study indicated no significant effect on physicochemical properties of films kept at 40°C and 75% RH for 3 months. Overall CS/MMT composite transdermal films exhibited improved mechanical and sustained drug release properties.

Pharmacological modulation of leukotriene D4 attenuates the development of opioid dependence in a mouse model of naloxone-induced opioid withdrawal syndrome

The present study was designed to investigate the effect of montelukast sodium, a leukotriene D(4) receptor antagonist, and 1,2,3,4,tetrahydroisoquinoline, a leukotriene D(4) synthetic pathway inhibitor, on the development of morphine dependence in a mouse model of naloxone-induced opioid withdrawal syndrome. Morphine (5 mg/kg, i.p.) was administered twice daily for a period of 5 days following which a single injection of naloxone (8 mg/kg, i.p.) precipitated the opioid withdrawal syndrome in mice. Behavioral observations were made for a period of 30 min immediately after naloxone treatment. The withdrawal syndrome was quantitatively assessed in terms of withdrawal severity score and the frequency of jumping, rearing, fore paw licking and circling. Montelukast sodium as well as 1,2,3,4,tetrahydroisoquinoline, markedly and dose dependently (p<0.01) attenuated the morphine-naloxone-induced opioid withdrawal syndrome in mice. However, administration of montelukast sodium or 1,2,3,4,tetrahydroisoquinoline did not alter the activity of the central nervous system, assessed in terms of locomotor activity count thus ruling out any per se sedative action of montelukast sodium. Further, pretreatment with montelukast sodium or 1,2,3,4,tetrahydroisoquinoline did not alter the acute analgesic effect of morphine. Thus, leukotriene D(4) may be involved in the development of opioid dependence and the precipitation of its withdrawal syndrome and thus may serve as a viable pharmacological target to tackle the problem of opioid addiction.

Lallemantia reylenne seeds as superdisintegrant: Formulation and evaluation of nimesulide orodispersible tablets

Aim: Orodispersible tablets also known as fast dissolving tablets disintegrate instantaneously within the mouth and thus can be consumed without water. The present study was aimed to formulate orodispersible tablets of nimesulide by using Lallemantia reylenne seeds as natural superdisintegrant. Materials and Methods: Powdered lallemantia seeds were characterized for powder flow properties (bulk density, tapped density, carrs consolidation index, hausner ratio, angle of repose), swelling index, viscosity, pH, and loss on drying. The prepared tablets were evaluated for different tablet parametric tests, wetting time, water absorption ratio, effective pore radius, porosity, packing fraction, in vitro and in vivo disintegration time, in vitro dissolution and stability studies. Results and Discussion: Increase in Lallementia reylenne concentration had an appreciable effect on tablet hardness and friability which clearly indicated binding potential of the seeds. Water absorption ratio increased with increase in Lallemantia reylenne concentration from batch A1 to A4. Water uptake coupled natural polymer swelling could be the most probable mechanism for concentration dependent reduction in disintegration time by the Lallemantia reylenne seeds. Porosity of the formulated tablets was found to increase from batch A1-A4. The in vitro disintegration results were in line with in vivo disintegration results. Conclusion: It could be concluded that Lallemantia reylenne seeds could be used as natural superdisintegrant in the formulation of orodispersible tablets.