Formulation and in vitro characterization of cefpodoxime proxetil gastroretentive microballoons

Background and the purpose of the study

The objective of the present work was to improve bioavailability of cepodoxime proxetil through gastroretentive microballoon formulation.

Methods

Microballoons of cefpodoxime proxetil were formulated by solvent evaporation and diffusion method employing hydroxypropylmethyl cellulose (HPMC) and ethyl cellulose (EC) polymers and characterized for particle size, surface morphology, incorporation efficiency, floating behavior, in vitro drug release study and differential scanning calorimetry (DSC).

Results

The average particle size of formulated microballoons was in the range of 54.23±2.78–95.66±2.19µm. Incorporation efficiencies of over 83.77±0.85% were achieved for the optimized formulations. Most of formulations remained buoyant (having buoyancy percentage maximum of 81.36±1.96%) for more than 12 hrs indicating good floating behavior of microballoons. Higher values of correlation coefficients were obtained with Higuchi''s square root of time kinetic treatment heralding diffusion as predominant mechanism of drug release.

Conclusion

Inferences drawn from in vitro studies suggest that microballoons may be potential delivery system for cefpodoxime proxetil with improvement in bioavailability in comparison to conventional dosage forms.     

Preparation and evaluation of sustained release microballoons of propranolol

Background and the purpose of the study

The purpose of the present investigation was to characterize, optimize and evaluate microballoons of Propranolol hydrochloride and to increase its boioavailability by increasing the retention time of the drug in the gastrointestinal tract.

Methods

Propranolol hydrochloride-loaded microballoons were prepared by the non-aqueous O/O emulsion solvent diffusion evaporation method using Eudragit RSPO as polymer. It was found that preparation temperature determined the formation of cavity inside the microballoon and this in turn determined the buoyancy. Microballoons were subjected to particle size determination, micromeritic properties, buoyancy, entrapment efficiency, drug loading, in vitro drug release and IR study. The correlation between the buoyancy, bulk density and porosity of microballoons were elucidated. The release rate was determined in simulated gastric fluid (SGF) of pH 1.2 at 37±0.5°C.

Results

The microballoons presented spherical and smooth morphologies (SEM) and were porous due to presence of hollow cavity. Microballoons remained buoyant for >12 hrs for the optimized formulation. The formulation demonstrated favorable in vitro floating and release characteristics. The encapsulation efficiency was high. In vitro dissolution kinetics followed the Higuchi model. The drug release from microballoons was mainly controlled by diffusion and showed a biphasic pattern with an initial burst release, followed by sustained release for 12 hrs. The amount of the drug which released up to 12 hrs was 82.05±0.64%. Statistical analysis (ANOVA) showed significant difference (p<0.05) in the cumulative amount of drug released after 30 min, and up to 12 hrs from optimized formulations.

Conclusion

The designed system for propanolol would possibly be advantageous in terms of increased bioavailability and patient compliance.     

An Investigation into Formulation and Processing Strategies to Drive Gastroretention of Gabapentin Tablets

Purpose

The aim of the present work was to develop gastroretentive drug delivery system of gabapentin from different matrices prepared by hot melt or conventional wet granulation, which may enhance drug bioavailability. The influence of core type, granulation process, and coating level on the drug release rates was investigated.

Methods

Tablet cores were prepared from hydrophilic system of hypermellose, carboxy melthyl celloulse, and Avicel or hydrophobic system of ethyl cellulose, alginic acid, and stearic acid. The tablets were coated by Eudragit RL with triethyl citrate and compressed directly. These tablets were evaluated according to their in vitro dissolution profiles and release mechanisms.

Results

Hydrophobic matrices allowed the control of drug release. Hot melt granulation was an effective tool over wet granulation or coating for slowing release rates from hydrophobic tablets. Both hydrophobic polymer ratio and coating level influenced the drug release mechanism. The drug release of samples with minor proportion of ethyl cellulose and stearic acid or low Eudragit RL level was driven by anomalous transport and the increase of their proportions contributed to the erosion of the matrix.

Conclusions

Hydrophobic core tablet prepared from hot melt granulation and coated by Eudragit RL has shown to be a promising formulation intended to gastroretentive gabapentin delivery system.

     

Formulation and In Vitro evaluation of pH sensitive oil entrapped polymeric blended gellan gum buoyant beads of clarithromycin

Background and the purpose of the study

A gastroretentive pH sensitive system has been a frontier approach to release the drug in controlled manner in stomach and duodenum. The aim of this study was to develop buoyant beads of gellan based, wherein, the oil was entrapped, blended with hydroxypropyl methyl cellulose or carbopol 934 in order to evaluate its potential for targeted sustained delivery of clarithromycin in the gastric region.

Methods

Buoyant beads of gellan was developed by inotropic gelation technique using calcium carbonate as gas forming agent and the drug polymer dispersion was emulsified with mineral oil. The oil was entrapped and blended with hydroxypropyl methyl cellulose or carbopol 934. The developed beads were evaluated in terms of diameter,% floating, encapsulation efficiency, In vitro drug release, In vivo gastric residence efficacy and clarithromycine concentration in the mucosa of the experimental animal model.

Results

The scanning electron microscope photograph indicated that the prepared beads were spherical in shape and buoyancy, encapsulation efficiency and drug content obtained from all batches were satisfactory. Particle size and percentage buoyancy of the gel beads increased by raising the concentration of calcium carbonate. The formulation exhibited sustained release profile and was best fitted in the Peppas model with n<0.45. Subsequent coating of microbeads exhibited zero-order sustained pattern of the drug release up to 8 hrs. Batch B₄ showed comparatively better residence and the drug concentration in the gastric mucosa of the treated animals.

Conclusion

The result provides evidence that the prepared optimized formulation may be used effectively for pH sensitive gastric targeted antibiotic such as clarithromycin.     

Nanotechnology in oncology: Characterization and in vitro release kinetics of cisplatin-loaded albumin nanoparticles: Implications in anticancer drug delivery

Context:

Nanotechnology is an empowering technology that holds promise in cancer therapeutics by increasing the ratio of tumor control probability to normal tissue complication probability. It can increase the bioavailability of the drug at the target site, reduce the frequency of administration and reach otherwise lesser-accessible sites. The present study shows the feasibility of the cisplatin-loaded albumin nanoparticle as a sustained delivery system.

Aims:

Cisplatin is one of the most widely used chemotherapeutic agents for the treatment of malignant disorders. Conventional cisplatin formulation given as intravenous infusion has low bioavailability to the target organ in addition to significant side-effects, like ototoxicity and nephrotoxicity. The aim of this study was to develop a protein-based nanoparticulate system for sustained release of cisplatin.

Materials and Methods:

Nanoparticles were prepared by the coacervaton method of microcapsulation and chemical cross-linking with glutaraldehyde. Particle size was characterized by dynamic light scattering and transmission electron microscopy.

Results and Conclusions:

Using the coacervation method, nanoparticles of less than 70 nm diameter were produced. Drug encapsulation measured by ultraviolet spectroscopy varied from 30% to 80% for different ratios of cisplatin and protein. In vitro release kinetics shows that the nanoparticle-based formulation has biphasic release kinetics and is capable of sustained release compared with the free drug (80% release in 45 h). The study proves the feasibility of the albumin-based cisplatin nanoparticle formulation as a sustained release vehicle of cisplatin.     

Preparation and evaluation of pellets using acacia and tragacanth by extrusion-spheronization

Background and the purpose of the study

Extrusion-spheronization is an established technique for the production of pellets for pharmaceutical applications. In this study, the feasibility and influence of the incorporation of acacia, by itself and in combination with tragacanth, on the ability of formulations containing 2 model of drugs (ibuprofen and theophylline) to form spherical pellets by extrusion-spheronization was investigated.

Material and Methods

Formulations containing different ratios of acacia and tragacanth (8:2, 9:1, and 10:0) and different drug concentrations (20%, 40%, and 60%) were prepared, on the basis of a 3² full factorial design. Pellet properties, such as aspect ratio, sphericity (image analysis), crushing strength and elastic modulus (mechanical tests), mean dissolution time, and dissolution profiles were evaluated. The effect of particular factors on responses was determined by linear regression analysis.

Results

The sphericity, drug release rate, and the mechanical properties of the pellets were affected by the amounts and types of the drugs, and the ratio of the gums. Acacia, relative to tragacanth, produced pellets with higher mechanical strength and a faster drug release rate. Addition of small amounts of tragacanth to ibuprofen formulations resulted in matrix pellets with slow drug release.

Conclusion

The results showed that acacia and tragacanth can be used successfully as 2 natural binders in the pellet formulations.     

Investigation on in vitro dissolution rate enhancement of indomethacin by using a novel carrier sucrose fatty acid ester

Background and the purpose of the study

The purpose of the present investigation was to characterize and evaluate solid dispersions (SD) of indomethacin by using a novel carrier sucrose fatty acid ester (SFE 1815) to increase its in vitro drug release and further formulating as a tablet.

Methods

Indomethacin loaded SD were prepared by solvent evaporation and melt granulation technique using SFE 1815 as carrier in 1:0.25, 1:0.5 1:0.75 and 1:1 ratios of drug and carrier. Prepared SD and tablets were subjected to in vitro dissolution studies in 900 mL of pH 7.2 phosphate buffer using apparatus I at 100 rpm. The promising SD were further formulated as tablets using suitable diluent (DCL 21, Avicel PH 102 and pregelatinised starch) to attain the drug release similar to that of SD.. The obtained dissolution data was subjected to kinetic study by fitting the data into various model independent models like zero order, first order, Higuchi, Hixon-Crowell and Peppas equations. Drug and excipient compatibility studies were confirmed by fourier transform infrared spectroscopy, X-ray diffraction, differential scanning calorimetry and scanning electron microscopy.

Results

The in vitro dissolution data exhibited superior release from formulation S₆ with 1:0.5 drug and carrier ratio using solvent evaporation technique than other SDs prepared at different ratio using solvent evaporation and melt granulation technique. The in vitro drug release was also superior to that of the physical mixtures prepared at same ratio and also superior to SD prepared using common carriers like polyvinyl pyrollidone and PEG 4000 by solvent evaporation technique. Tablets (T₈) prepared with DCL21 as diluent exhibited superior release than the other tablets. The tablet formulation (T₈) followed first order release with Non-Fickian release.

Conclusion

SFE 1815 a novel third generation carrier can be used for the preparation of SD for the enhancement of in vitro drug release of indomethacin an insoluble drug belonging to BCS class II.     

Formulation and in vitro characterization of domperidone loaded solid lipid nanoparticles and nanostructured lipid carriers

Background and the purpose of the study

Domperidone (DOM) is a dopamine- receptor (D₂) antagonist, widely used in the treatment of motion-sickness. The pharmacokinetic parameters of DOM make it a suitable candidate for development of Solid Lipid Nanoparticle (SLN) and Nanostructured Lipide Carrier (NLC). The purpose of the present investigation was to prepare and evaluate DOM loaded solid lipid nanoparticles (DOM-SLN) and DOM loaded nanostructured lipid carriers (DOM-NLC).

Methods

DOM loaded SLN and NLC were prepared by hot homogenization followed by ultrasonication technique, using trimyristin as solid lipid, cetyl recinoleate as liquid lipid and a mixture of soy phosphatidylcholine (99%) and tween 80 as surfactant. SLN and NLC were characterized for particle size, polydispersity index (PDI), zeta potential and entrapment efficiency. The effects of composition of lipid materials and surfactant mixture on the particle size, PDI, zeta potential, drug entrapment efficiency, and in vitro drug release behavior were investigated. DSC analysis was performed to characterize the state of drug and lipid modification. Shape and surface morphology were determined by transmission electron microscopy (TEM). SLN and NLC formulations were subjected to stability study over a period of 40 days.

Results

The mean particle size, PDI, zeta potential and entrapment efficiency of optimized SLN (SLN1) and NLC were found to be 30.45 nm, 0.156, 12.40 mV, 87.84% and 32.23 nm, 0.160, 10.47 mV, 90.49% respectively. DSC studies revealed that DOM was in an amorphous state and triglycerides were in the β prime form in SLN and NLC. Shape and surface morphology was determined by TEM revealed fairly spherical shape of nanoparticles. In vitro release studies demonstrated that both the SLN and NLC formulations possessed a controlled release over a period of 24 hrs. SLN and NLC formulations were subjected to stability over a period of 40 days. There was no significant (P<0.05) change in particle size, zeta potential, PDI and entrapment efficiency indicating the developed SLN and NLC were fairly stable.

Conclusion

Fairly spherical shaped, stable and controlled release DOM-SLN and DOM-NLC could be prepared by hot homogenization followed by ultrasonication technique.     

Development of diclofenac sodium-loaded alginate-PVP K 30 microbeads using central composite design

Background and the purpose of the study

Diclofenac sodium is a non-steroidal anti-inflammatory agent with a short biological half-life (1–2 hr) and requires multiple dosing. This research was carried out to develop and optimize diclofenac sodium loaded alginate-PVP K 30 microbeads to eliminate the need for multiple dosing and adverse effects.

Methods

Diclofenac sodium loaded alginate-PVP K 30 microbeads were prepared by ionotropic gelation. Particle size, drug release, swelling, FTIR and SEM analyses were performed.

Results

Optimized microbeads showed particle size of 0.589±0.054 to 0.620±0.067 mm, and drug entrapment efficiency of 97.88±2.86 to 98.60±3.55%. The in vitro drug release from microbeads was sustained over 10 hrs and followed controlled-release pattern. FTIR analysis indicated the possibility of intermolecular hydrogen bonding interactions, i.e., –OH…O=C in microbeads.

Conclusion

Microbeads for oral controlled delivery of diclofenac sodium were successfully developed by ionotropic gelation.     

Comparative in vitro and in vivo evaluation of three tablet formulations of amiodarone in healthy subjects

Background and the purpose of the study

The relative in vivo bioavailability and in vitro dissolution studies of three chemically equivalent amiodarone generic products in healthy volunteers was evaluated in three separate occasions. The possibility of a correlation between in vitro and in vivo performances of these tablet formulations was also evaluated.

Methods

The bioequivalence studies were conducted based on a single dose, two-sequence, cross over randomized design. The bioavailability was compared using AUC_0–72, AUC_0–8, C_max and T_max. Similarity factor, dissolution efficiency (DE), and mean dissolution time (MDT) was used to compare the dissolution profiles. Polynomial linear correlation models were tested using either MDT vs mean residence time (MRT) or fraction of the drug dissolved (FRD) vs fraction of the drug absorbed (FRA).

Results

Significant differences were found in the dissolution performances of the tested formulations and therefore they were included in the development of the correlation. The 90% confidence intervals of the log-transformed AUC0-72, AUC_0–8, and C_max of each two formulations in each bioequivalence studies were within the acceptable range of 80–125%. Differences were not observed between the untransformed T_max values. Poor correlation was found between MRT and MDT of the products. A point-to-point correlation which is essential for a reliable correlation was not obtained between pooled FRD and FRA. The dissolution condition which was used for amiodarone tablets failed for formulations which were bioequivalent in vivo and significant difference between the dissolution characteristics of products (f2<50) did not reflect their in vivo properties.

Major conclusions

Bioequivalence studies should be considered as the only acceptable way to ensure the interchangeability and in vivo equivalence of amiodarone generic drug products. The dissolution conditions used of the present study could be used for routine and in-process quality control of amiodarone tablet formulations.     

Enhance transdermal delivery of flurbiprofen via microemulsions: Effects of different types of surfactants and cosurfactants

Background and the purpose of the study

Microemulsions are thermodynamically stable, clear dispersions of water, oil, surfactant, and cosurfactant. This study was aimed to develop flurbiprofen microemulsion for enhanced transdermal delivery and investigate the effects of different surfactants and cosurfactants on its delivery and phase behavior.

Method

Various surfactant-cosurfactant mixtures in ratio of 2:1 (Smix) along with oleic acid (oil) were selected and phase diagrams were constructed. Six microemulsions each containing 5% drug, 5% oil, 56% Smix and 34% water, were prepared and compared for their permeation and phase behaviors to determine the effects of the type of Smix.

Results

In vitro transdermal permeation through rabbit skin of all microemulsions was high than saturated aqueous drug solution. Tween 20 and ethanol as Smix produced the highest flux amongst all the Smix, and were used to prepare formulations with different values of oil and Smix. While the type of surfactant did not affect the droplet size, propylene glycol as cosurfactant produced the largest droplets and highest viscosity. Decrease in oil or Smix concentration resulted in decrease of the droplet size and increase in permeation flux while decrease in viscosity also increased the permeation flux of microemulsions. Finally the selected microemulsion formulation comprising 5% flurbiprofen, 5% oleic acid, 46% Tween 20:ethanol (2:1) and 44% water, showed the highest transdermal flux and caused no skin irritation.

Conclusion

Type of surfactant and cosurfactant affect both the phase behavior and transdermal drug delivery of microemulsion; and results of this study showed that they are promising vehicles for improved transdermal delivery and sustained action of flurbiprofen.     

Unraveling the cytotoxic potential of Temozolomide loaded into PLGA nanoparticles

Background

Nanotechnology has received great attention since a decade for the treatment of different varieties of cancer. However, there is a limited data available on the cytotoxic potential of Temozolomide (TMZ) formulations. In the current research work, an attempt has been made to understand the anti-metastatic effect of the drug after loading into PLGA nanoparticles against C6 glioma cells.Nanoparticles were prepared using solvent diffusion method and were characterized for size and morphology. Diffusion of the drug from the nanoparticles was studied by dialysis method. The designed nanoparticles were also assessed for cellular uptake using confocal microscopy and flow cytometry.

Results

PLGA nanoparticles caused a sustained release of the drug and showed a higher cellular uptake. The drug formulations also affected the cellular proliferation and motility.

Conclusion

PLGA coated nanoparticles prolong the activity of the loaded drug while retaining the anti-metastatic activity.     

QTc interval prolongation by fexofenadine in healthy human volunteers and its correlation with plasma levels of fexofenadine: A demonstration of anticlockwise hysteresis

Aim:

The study was designed to establish relationship between the plasma concentration and QTc interval prolonging effect of fexofenadine and demonstrate the phenomenon of anticlockwise hysteresis.

Materials and Methods:

Six subjects were given fexofenadine 60 mg tablet orally under stable conditions, and their drug concentrations were measured at regular intervals. At predetermined time, their ECGs were recorded. Data were analyzed and plotted graphically.

Design and Setting:

Randomized parallel design, single group study conducted at clinical research organization of Ahmadabad.

Results:

In all subjects time taken for maximum plasma concentration of fexofenadine (T_max) was around 3 h and the value of average maximum plasma concentration was 460.63 ng/mL, the effect of fexofenadine on the heart (measured as QTc interval prolongation) was maximum (E_max) after 6 h and average QTc interval was 469.75 ms. Thus, the time to maximum concentration of fexofenadine did not match with the maximum effect on the heart as measured by QTc interval.

Conclusion:

The relationship between the drug concentration and drug effect on the heart are at two different time scales. It can be understood by two-compartment model of pharmacokinetics, and this retardation or lagging of an effect behind the concentration is known as hysteresis. The increase of QTc was not beyond 500 ms and not sustained, demonstrating overall cardiac safety of fexofenadine.     

Repaglinide-loaded solid lipid nanoparticles: effect of using different surfactants/stabilizers on physicochemical properties of nanoparticles

Background

Repaglinide is an efficient anti-diabetic drug which is prescribed widely as multi-dosage oral daily regimens. Due to the low compliance inherent to each multi-dosage regimen, development of prolonged-release formulations could enhance the overall drug efficacy in patient populations.

Methods

Repaglinide-loaded solid lipid nanoparticles (SLNs) were developed and characterized in vitro. Various surfactants were used in this study during the nanocarrier preparation procedure and their corresponding effects on some physicochemical properties of SLNs such as size, zeta potential; drug loading parameters and drug release profiles was investigated. Stearic acid and glyceryl mono stearate (GMS) were used as lipid phase and phosphatidylcholin, Tween80, Pluronic F127, poly vinyl alcohol (PVA) and polyvinyl pyrrolidone (PVP) were used as surfactant/stabilizer.

Results

The results showed some variations between formulations; where the Tween80-based SLNs showed smallest size, the phosphatidylcholin-based SLNs indicated most prolonged drug release time and the highest loading capacity. SEM images of these formulations showed morphological variations and also confirmed the nanoscale size of these particles. The FTIR and DSC results demonstrated no interaction between drug and excipients. The invitro release profiles of different formulations were studied and observed slow release of drug from all formulations. However significant differences were found among them in terms of their initial burst release as well as the whole drug release profile. From fitting these data to various statistical models, the Peppas model was proposed as the best model to describe the statistical indices and, therefore, mechanism of drug release.

Conclusion

The results of this study confirmed the effect of surfactant type on SLNs physicochemical properties such as morphological features, loading parameters, particle sizes and drug release kinetic. With respect to the outcome data, the mixture of phosphatidylcholin/Pluronic F127 was selected as the best surfactant/stabilizer to coat the lipid core comprising stearic acid and GMS.     

The release behavior and kinetic evaluation of tramadol HCl from chemically cross linked Ter polymeric hydrogels

Background and the purpose of the study

Hydrogels, being stimuli responsive are considered to be effective for targeted and sustained drug delivery. The main purpose for this work was to study the release behavior and kinetic evaluation of Tramadol HCl from chemically cross linked ter polymeric hydrogels.

Methods

Ter-polymers of methacrylate, vinyl acetate and acrylic acid cross linked with ethylene glycol dimethacrylate (EGDMA) were prepared by free radical polymerization. The drug release rates, dynamic swelling behavior and pH sensitivity of hydrogels ranging in composition from 1-10 mol% EGDMA were studied. Tramadol HCl was used as model drug substance. The release behavior was investigated at pH 8 where all formulations exhibited non-Fickian diffusion mechanism.

Results and major conclusion

Absorbency was found to be more than 99% indicating good drug loading capability of these hydrogels towards the selected drug substance. Formulations designed with increasing amounts of EGDMA had a decreased equilibrium media content as well as media penetrating velocity and thus exhibited a slower drug release rate. Fitting of release data to different kinetic models indicate that the kinetic order shifts from the first to zero order as the concentration of drug was increased in the medium, showing gradual independency of drug release towards its concentration. Formulations with low drug content showed best fitness with Higuchi model whereas those with higher concentration of drug followed Hixson-Crowell model with better correlation values indicating that the drug release from these formulations depends more on change in surface area and diameter of tablets than that on concentration of the drug. Release exponent (n) derived from Korse-Meyer Peppas equation implied that the release of Tramadol HCl from these formulations was generally non-Fickian (n > 0.5 > 1) showing swelling controlled mechanism. The mechanical strength and controlled release capability of the systems indicate that these co-polymeric hydrogels have a great potential to be used as colon drug delivery device through oral administration.     

Formulation development and rheological studies of palatable cefetamet pivoxil hydrochloride dry powder suspension

Background and the purpose of the study

Because of its intense bitter taste and susceptibility to moisture Cefetamet Pivoxil (CPH) is presently available only in the form of tablet. The aim of this study was to develop taste masked CPH dry powder suspension.

Methods

Methods employed for formulations were: a) Film coating of CPH using Eudragit E100 and subsequent adsorption on different carriers such as spray-dried lactose, sodium starch glycolate and spray-dried mannitol and b) Complexation of CPH with three different ion exchange resins indion 234 amberlite IRP64 and amberlite IRP69.

Results

Taste viz evaluation as recognized by volunteers revealed that coating with Eudragit E100 and subsequent adsorption on different carriers do not mask the bitter taste of the drug. Suspensions prepared using amberlite IRP64 and amberlite IRP69 were extremely palatable with no bitter after taste. They showed pseudoplastic flow behavior and were too viscous even after shearing for sufficient duration of time and exhibited poor pourability. The suspension made with indion 234 was palatable with slight or no bitter after taste. It demonstrated plastic flow with negligible thixotropy. It had moderate viscosity at rest and could be poured after a reasonable amount of shaking. CPH dry powder suspensions were very unstable under different conditions except under refrigeration. A 5% degradation of drug was occurred in reconstituted suspension in 4 days period when stored at room temperature.

Conclusion

Dry powder suspension prepared with indion 234 having 5% overages was stable even after 4th day of reconstitution and palatable with slight or no bitter after taste.     

Cost-effectiveness analysis of baclofen and chlordiazepoxide in uncomplicated alcohol-withdrawal syndrome

Objectives:

Benzodiazepines (BZDs) are the first-line drugs in alcohol-withdrawal syndrome (AWS). Baclofen, a gamma-aminobutyric acid_B (GABA_B) agonist, controls withdrawal symptoms without causing significant adverse effects. The objective of this study was to compare the cost-effectiveness of baclofen and chlordiazepoxide in the management of uncomplicated AWS.

Materials and Methods:

This was a randomized, open label, standard controlled, parallel group study of cost-effectiveness analysis (CEA) of baclofen and chlordiazepoxide in 60 participants with uncomplicated AWS. Clinical efficacy was measured by the Clinical Institute Withdrawal Assessment for alcohol (CIWA-Ar) scores. Lorazepam was used as supplement medication if withdrawal symptoms could not be controlled effectively by the study drugs alone. Both direct and indirect medical costs were considered and the CEA was analyzed in both patient''s perspective and third-party perspective.

Results:

The average cost-effectiveness ratio (ACER) in patient''s perspective of baclofen and chlordiazepoxide was Rs. 5,308.61 and Rs. 2,951.95 per symptom-free day, respectively. The ACER in third-party perspective of baclofen and chlordiazepoxide was Rs. 895.01 and Rs. 476.29 per symptom-free day, respectively. Participants on chlordiazepoxide had more number of symptom-free days when compared with the baclofen group on analysis by Mann-Whitney test (U = 253.50, P = 0.03).

Conclusion:

Both study drugs provided relief of withdrawal symptoms. Chlordiazepoxide was more cost-effective than baclofen. Baclofen was relatively less effective and more expensive than chlordiazepoxide.KEY WORDS: Alcohol-withdrawal syndrome, baclofen, chlordiazepoxide, clinical institute withdrawal assessment for alcohol, cost-effectiveness analysis     

Formulation of inhalable lipid-based salbutamol sulfate microparticles by spray drying technique

Background

The aim of this work was to develop dry powder inhaler (DPI) formulations of salbutamol sulfate (SS) by the aid of solid lipid microparticles (SLmPs), composed of biocompatible phospholipids or cholesterol.

Methods

The SLmPs were prepared by using two different solvent systems (ethanol and water-ethanol) and lipid carriers (dipalmitoylphosphatidylcholine (DPPC) and cholesterol) with/without L-leucine in the spray drying process. The spray-dried microparticles were physically-mixed with coarse lactose monohydrate in order to make our final DPI formulations and were investigated in terms of physical characteristics as well as in vitro drug release profile and aerosolization behavior.

Results

We observed significant differences in the sizes, morphologies, and in vitro pulmonary depositions between the formulations. In particular, the SS-containing SLmPs prepared with water-ethanol (30:70 v/v) solution of DPPC and L-leucine which had then been blended with coarse lactose (1:9 w/w) exhibited the highest emitted dose (87.9%) and fine particle fraction (42.7%) among the formulations. In vitro drug release study indicated that despite of having a significant initial burst release for both cholesterol and DPPC-based microparticles, the remained drug released more slowly than the pure drug.

Conclusion

This study demonstrated the potential of using lipid carriers as well as L-leucine in DPI formulations of SS to improve its aerosolization behavior and retard the release profile of the drug.     

Formualtion and evaluation of floating drug delivery system containing clarithromycin for Helicobacter pylori

Floating matrix tablets are designed to prolong the gastric residence time after oral administration, at a particular site and controlling the release of drug especially useful for achieving controlled plasma level as well as improving bioavailability. With this objective, floating dosage form containing clarithromycin as drug was designed for the treatment of Helicobacter pylori. Tablets containing hydroxypropylmethylcellulose (HPMC), drug and different additives were compressed using wet granulation and D-optimal design technique. The study shows that tablet composition and mechanical strength have great influence on the floating properties and drug release. Incorporation of gas-generating agent together with polymer improved drug release, besides optimal floating (floating lag time < 30 s; total floating time > 10 h). The drug release was sufficiently sustained (more than 8 h) and anomalous diffusion as well as zero-order was confirmed. Optimization of the evaluating parameters with 'design expert' software was employed to get final optimized formulation. The optimized formulation was obtained using 62.5% clarithromycin, 4.95% HPMC K15M, 18.09% HPMC K4M, 12.96% sodium bicarbonate which gave floating lag time < 30 s with a total floating time > 10 h, in vitro release profile very near to the target in vitro release profile and follows anomalous diffusion as well as zero order pattern of release.     

Preparation of Coated Valproic Acid and Sodium Valproate Sustained-release Matrix Tablets

The aim of this research was to investigate the technique for preparation of coated valproic acid and sodium valproate sustained-release matrix tablets. Different diluents were tested and selected as the effective absorbent for oily valproic acid. Effect of the amount of absorbent and hydroxypropylmethylcellulose on drug release from valproic acid-sodium valproate matrix tablets prepared with wet granulation technique was evaluated in pH change system. Colloidal silicon dioxide effectively adsorbed liquid valproic acid during wet granulation and granule preparation. The amounts of colloidal silicon dioxide and hydroxypropylmethylcellulose employed in tablet formulations affected drug release from the tablets. The drug release was prominently sustained for over 12 h using hydroxypropylmethylcellulose-based hydrophilic matrix system. The mechanism of drug release through the matrix polymer was a diffusion control. The drug release profile of the developed matrix tablet was similar to Depakine Chrono^®, providing the values of similarity factor (f2) and difference factor (f1) of 85.56 and 2.37, respectively. Eudragit^® L 30 D-55 was used as effective subcoating material for core matrix tablets before over coating with hydroxypropylmethylcellulose film with organic base solvent. Drug release profile of coated matrix tablet was almost similar to that of Depakine Chrono^®.