Effect of Hypoproteinemia on Electrolyte Measurement by Direct and Indirect Ion Selective Electrode Methods.

Objective The aim of this study was to see the effect of hypoproteinemia on electrolyte measurement by two different techniques, that is, direct ion selective electrode (ISE) and indirect ISE. Material and Method It was an observational study in which 90 serum samples with normal protein content (Group-1) were subjected to sodium (Na + ) and potassium (K + ) measurements by direct and indirect ISE methods. In the same way, 90 serum samples with total protein < 5 g/dL (Group-2) were subjected to Na + and K + measurements by direct and indirect ISE methods. Result In samples from Group-1 patients, average Na + was 138.1 ± 4.764 mmol/L by direct ISE method and 139.3 ± 3.887 mmol/L by indirect ISE method while average K + was 4.41 ± 0.644 mmol/L by direct ISE method and 4.40 ± 0.592 mmol/L by indirect ISE method. There was no statistically significant difference in Na + and K + values measured by different methods. In samples from Group-2 patients, measured value of Na + by direct ISE and indirect ISE was 134.57 ± 5.520 mmol/L and 138.64 ± 5.401 mmol/L, respectively. Difference between these two values was statistically significant with p -value of < 0.0001, but direct ISE and indirect ISE measured values of K + was 4.146 ± 0.9639 mmol/L and 4.186 ± 0.8989, respectively, with no significant difference. Conclusion Direct and indirect ISE methods are not comparable and showing significantly different results for Na + in case of hypoproteinemia. So, it is recommended that setups like intensive care unit or emergency department, where electrolyte values have significant treatment outcome, should follow direct ISE method and should compare its previous result with the same method. Both the methods should not be used interchangeably.

Fabrication and evaluation of fast disintegrating pellets of cilostazol.

The present study was designed to formulate and develop fast disintegrating pellets of poorly soluble model drug (cilostazol) by reducing the proportion of micro-crystalline cellulose with pre-gelatinized starch (PGS), lactose and chitosan. The bioavailability enhancement of a model drug was achieved by preparing inclusion complex with Captisol® (Sulfobutyl Ether ß cyclodextrin - SBE-ß-CD). Extrusion-spheronization technique was used to formulate pellets. Placket-Burman design was used for the initial screening of most significant factors such as screen size (mm), ratio of micro crystalline cellulose: PGS + lactose + chitosan and % of HPMC which affects pellet properties. The inclusion complex of drug and Captisol® (SBE-ß-CD) was prepared by Solvent Evaporation method and were incorporated into pellets in a predefined proportion. Formulation was optimized by using 32 full factorial design, the optimized batch was selected on the basis of dependent variables such as % yield, pellet size, disintegration time and % Cumulative drug release (%CDR), the obtained results were 87.15%, 0.75 mm, 13 min and 91.024% respectively. Differential scanning calorimetry (DSC) and Fourier transform infrared spectrometry (FTIR) study revealed no significant interaction between drug and polymer. Scanning electron microscopy (SEM) confirmed uniform and spherical shaped pellets having pores on the surface which facilitates wicking action and fast disintegrating property of pellets. A design space was constructed to meet the desirable target and optimized batch. The scope of study can further extended to hydrophobic molecules which may useful due to rapid disintegration and enhanced dissolution rate.

A Review on Enteric Coated Pellets Composed of Core Pellets Prepared by Extrusion-Spheronization.

Enteric coated dosage form bypasses the stomach and releases the drug into the small intestine. Advantages of enteric coated pellets in comparison with enteric coated tablets are a) Pellets provide rapid onset of action and faster drug release due to the smaller size than tablets and b) Pellets exhibit less residence time of acid-labile drugs in the stomach compared to tablets. Dosage form coat can be damaged by longer resistance time in the stomach. The present review summarizes the current state of enteric coated pellets where core pellets are prepared by extrusion-spheronization technique and the enteric coating is applied in a fluidized bed processor. Two approaches are involved in the preparation of core pellets. In the first approach, a mixture of drug and excipient(s)/co-processed excipient is passed through extruders to prepare core pellets. In the second approach, excipient core pellets are prepared by extrusion technique and the drug is layered onto it before the enteric coating. The excipients present in the core pellets decide immediate or extended release of drug in the intestine. The coprocessed excipient pellets provide less batch variability and provide a platform for layering of many drugs before enteric coating. Some patents included enteric coating pellets [CN105456223 (A), CN105596310 (A), CN105616371 (A), CN105663095 (A), CN101611766B, CN106511862 (A), CN106668018 (A), CN106727381 (A), CN106924222 (A), TW200624127 (A), US 2017/0165248A1, US 2017/0224720A1] are discussed.

Screening of Sacrificial Excipients for Arresting Devitrification of Itraconazole from Solid Dispersion.

OBJECTIVES: The aim of the present investigation was to develop a solid dispersion of itraconazole (ITR) using sacrificial excipients like pregelatinized starch and spray-dried lactose alongside hydroxypropyl methylcellulose and Poloxamer 188, thereby arresting the conversion of the amorphous form of ITR to crystalline form, and to assess the dissolution stability of an amorphous form of the drug during short-term storage. MATERIALS AND METHODS: ITR-loaded solid dispersions were prepared by kneading. Formulation optimization was achieved by using a 24 full factorial design on the basis of cumulative percent drug released at t30, t60, and t120 min. An artificial neural network (ANN) was also applied as a statistical tool for obtaining better predictive ability and the outcomes of the ANN were compared with that of Design-Expert software. RESULTS: The spectral data revealed no drug-carrier interactions. The P-X-ray diffraction study of the optimized batch showed a decrease in the crystallinity of drug as compared to the untreated drug. The in vitro dissolution studies of the optimized batch showed higher dissolution (92% at 120 min) in comparison to the other formulations. The dissolution stability study was performed at 40°C and 75% relative humidity for 90 days for the optimized formulation. The results of the optimized batch showed insignificant changes in cumulative percentage drug release during storage. CONCLUSION: Dissolution stability could be attributed to the presence of sacrificial excipients as they tend to absorb moisture during storage and possibly get converted into crystalline form, thereby minimizing the recrystallization of ITR.

Development of Biodegradable Injectable In situ Forming Implants for Sustained Release of Lornoxicam.

OBJECTIVE: The focus of this study was to develop in situ injectable implants of Lornoxicam which could provide sustained drug release. METHODS: Biodegradable in situ injectable implants were prepared by polymer precipitation method using polylactide-co-glycolide (PLGA). An optimized formulation was obtained on the basis of drug entrapment efficiency, gelling behavior and in vitro drug release. The compatibility of the formulation ingredients were tested by Fourier transform infrared (FT-IR) spectroscopy, and differential scanning colorimetry (DSC). SEM study was performed to characterize in vivo behavior of in situ implant. Pharmacokinetic study and in vivo gelling study of the optimized formulation were performed on Sprague-Dawley rats. Stability testing of optimized formulation was also performed. RESULTS: The drug entrapment efficiency increased and burst release decreased with an increase in the polymer concentration. Sustained drug release was obtained up to five days. SEM photomicrographs indicated uniform gel formation. Chemical interaction between the components of the formulation was not observed by FT-IR and DSC study. Pharmacokinetic studies of the optimized formulation revealed that the maximum plasma concentration (Cmax), time to achieve Cmax (Tmax) and area under plasma concentration curve (AUC) were significantly higher than the marketed intramuscular injection of lornoxicam. Stability study of optimized batch showed no change in physical and chemical characteristics. CONCLUSION: Lornoxicam can be successfully formulated as in situ injectable implant that provides long-term management of inflammatory disorders with improved patient compliance.

Development and Optimization of Dispersible Tablet of Bacopa monnieri with Improved Functionality for Memory Enhancement.

INTRODUCTION: The Bacopa monnieri is traditional Ayurvedic medicine, and reported for memory-enhancing effects. The Bacoside is poorly soluble, bitter in taste and responsible for the memory enhancement action. Memory enhancer is commonly prescribed for children or elder people. OBJECTIVE: Poor solubility, patient compliance and bitterness were a major driving force to develop taste masked ß-cyclodextrin complex and dispersible tablets. MATERIALS AND METHODS: The inclusion complex of Bacopa monnieri and ß-cyclodextrin was prepared in different molar ratios of Bacopa monnieri by Co-precipitation method. Phase solubility study was conducted to evaluate the effect of ß-cyclodextrin on aqueous solubility of Bacoside A. The characterization was determined by Fourier transformation infrared spectroscopy (FTIR),Differential scanning calorimetry (DSC) and X-ray diffraction study (XRD).Crospovidone and croscarmallose sodium were used as super disintigrant. The 32 full factorial design was adopted to investigate the influence of two superdisintegrants on the wetting time and disntegration time of the tablets. CONCLUSION: The result revels that molar ratio (1:4) of inclusion complex enhance 3-fold solubility. Full factorial design was successfully employed for the optimization of dispersible tablet of B. monnieri. The short-term accelerated stability study confirmed that high stability of B. monnieri in inclusion complex.

Formulation and Optimization of Multiparticulate Drug Delivery System Approach for High Drug Loading.

The aim of the present work was to develop and optimize multiparticulate formulation viz. pellets of naproxen by employing QbD and risk assessment approach. Mixture design with extreme vertices was applied to the formulation with high loading of drug (about 90%) and extrusion-spheronization as a process for manufacturing pellets. Independent variables chosen were level of microcrystalline cellulose (MCC)-X 1, polyvinylpyrrolidone K-90 (PVP K-90)-X 2, croscarmellose sodium (CCS)-X 3, and polacrilin potassium (PP)-X 4. Dependent variables considered were disintegration time (DT)-Y 1, sphericity-Y 2, and percent drug release-Y 3. The formulation was optimized based on the batches generated by MiniTab 17 software. The batch with maximum composite desirability (0.98) proved to be optimum. From the evaluation of design batches, it was observed that, even in low variation, the excipients affect the pelletization property of the blend and also the final drug release. In conclusion, pellets with high drug loading can be effectively manufactured and optimized systematically using QbD approach.

Serum fructosamine, serum glycated albumin and serum glycated ß-lipoprotein in type 2 diabetes mellitus patients with and without microvascular complications.

BACKGROUND: Glycation of serum proteins has been proposed as an important mechanism of complications of diabetes but whether there are differences in glycation of different serum proteins and whether it has any correlation with development of microvascular complications has not been studied in depth. This study aimed to assess level of serum fructosamine, glycated albumin and glycated ß-lipoprotein in type 2 diabetes mellitus patients with and without microvascular complications and to find out their correlation with diabetes complications. METHODS: Case-control study involving 150 individuals at a tertiary care hospital in western India. Fifty participants were healthy controls (group 1), 50 were type 2 diabetes patients without any evident microvascular complication (group 2) and 50 were type 2 diabetes patients with one or more microvascular complications (group 3). Serum fructosamine, FBS, PP2BS and other biochemical parameters were measured. Glycated albumin and glycated ß-lipoprotein were measured by agarose gel electrophoresis followed by NBT staining. Unpaired t-test was used to find out significance of difference between two groups and correlation coefficient to find out statistical correlation between two variables. RESULTS: Type 2 diabetes patients with one or more microvascular complications had poor glycemic control as indicated by markers of short and mid-term glycemia. Differences between the groups for fructosamine, glycated albumin and glycated ß-lipoprotein were significant (p < 0.001). Glycated albumin correlated with FBS, PP2BS and fructosamine in all diabetic patients (group 2 and 3) whereas glycated ß-lipoprotein correlated with these parameters only in group 3 and it was markedly elevated in group 3. CONCLUSION: Serum glycated ß-lipoprotein was disproportionately elevated compared to fructosamine and glycated albumin in diabetes patients with microvascular complications (group 3) and it correlated with rest of glycemic markers only in this group. Glycated ß-lipoprotein might help in identifying diabetic individuals at high future risk of developing microvascular complications.

Dissolution rate improvement of telmisartan through modified MCC pellets using 32 full factorial design.

Context: Microcrystalline cellulose (MCC) is the most widely used excipient for the production of pellets but it retards the release of poorly water soluble drugs. Objective: The present investigation reports incorporation of camphor, cross carmellose sodium (CCS) and spray dried lactose (SDL) into MCC pellets to enhance the dissolution rate of telmisartan. Materials and methods: A full factorial design (32) was used in the study. Concentration of camphor and CCS was selected as independent variables whereas percentage porosity and percentage drug release at 60 min were selected as dependent variables. Pellets were produced by extrusion-spheronization technique and evaluated for percentage yield, particle size analysis, flow characteristics, percentage porosity, drug content and in vitro drug release. Contour plots and 3-D surface plots were presented for graphical expression of the results. Results and discussion: Pellet formulations exhibited acceptable morphological, flow and mechanical properties. As against to 38.54% drug release after 60 min with MCC pellets, pellets prepared with optimized formulation, composed of proper combination of MCC, SDL, camphor and CCS, released 100% drug after 60 min. Conclusion: Our study underlines the fact that dissolution of telmisartan from MCC pellets can be successfully enhanced by incorporating water soluble excipient, disintegrant and pore formers.

Development and characterization of novel hydrogel containing antimicrobial drug for treatment of burns.

INTRODUCTION: The aim of burn management and therapy is fast healing and epithelisation to prevent infection. The present study is concerned with the development and characterization of a novel nanaoparticulate system; cubosomes, loaded with silver sulfadiazine (SSD) and Aloe vera for topical treatment of infected burns. METHODS: Cubosome dispersions were formulated by an emulsification technique using different concentrations of a lipid phase Glyceryl Monooleate (GMO) and Poloxamer 407. The optimum formulae were incorporated in an aloe vera gel containing carbopol 934, to form cubosomal hydrogels (cubogels). The cubogels were characterized by in vitro release of SSD, rheological properties, pH, bioadhesion, Transmission Electron Microscopy and in-vivo Wound Healing Study. RESULTS: The results show that the different concentration of GMO had significant effect on particle size, % EE and in vitro drug release. From the in-vitro drug release pattern and similarity factor (f2), it was concluded that batch CG3 (15% GMO and 1% P407) exhibited complete and controlled drug release within 12 hour (i.e. 98.25%), better bio adhesion and superior burn healing as compared to the marketed product. CONCLUSION: The in vivo burns healing study in rats revealed that the prepared optimized cubogel containing SSD and aloe vera has superior burns healing rate than cubogel with only SSD and marketed preparation so, it may be successfully used in the treatment of deep second degree burn.

Quality by Design (QbD) Approach for Development of Co-Processed Excipient Pellets (MOMLETS) By Extrusion-Spheronization Technique.

BACKGROUND: Microcrystalline cellulose (MCC) is an excellent excipient for the production of pellets by extrusion spheronization. However, it causes slow release rate of poorly water soluble drugs from pellets. Co-processed excipient prepared by spray drying (US4744987; US5686107; WO2003051338) and coprecipitation technique (WO9517831) are patented. OBJECTIVE: The objective of present study was to develop co-processed MCC pellets (MOMLETS) by extrusion-spheronization technique using the principle of Quality by Design (QbD). METHODS: Co-processed excipient core pellets (MOMLETS) were developed by extrusion spheronization technique using Quality by Design (QbD) approach. BCS class II drug (telmisartan) was layered onto it in a fluidized bed processor. RESULTS: Quality Target Product Profile (QTPP) and Critical Quality Attributes (CQA) for pellets were identified. Risk assessment was reported using Ishikawa diagram. Plackett Burman design was used to check the effect of seven independent variables; superdisintegrant, extruder speed, ethanol: water, spheronizer speed, extruder screen, pore former and MCC: lactose; on percentage drug release at 30 min. Pareto chart and normal probability plot was constructed to identify the significant factors. Box-Behnken design (BBD) using three most significant factors (Extruder screen size, type of superdisintegrant and type of pore former) was used as an optimization design. The control space was identified in which desired quality of the pellets can be obtained. CONCLUSION: Co-processed excipient core pellets (MOMLETS) were successfully developed by QbD approach. Versatility, Industrial scalability and simplicity are the main features of the proposed research.

Formulation and development of ophthalmic in situ gel for the treatment ocular inflammation and infection using application of quality by design concept.

CONTEXT: The conventional liquid ophthalmic delivery systems exhibit short pre-corneal residence time and the relative impermeability to the cornea which leads to poor ocular bioavailability. OBJECTIVE: The aim of this study was to apply quality by design (QbD) for development of dexamethasone sodium phosphate (DSP) and tobramycin sulfate (TS)-loaded thermoresponsive ophthalmic in situ gel containing Poloxamer 407 and hydroxyl propyl methyl cellulose (HPMC) K4M for prolonging the pre-corneal residence time, ocular bioavability and decreases the frequency of administration of dosage form. The material attributes and the critical quality attributes (CQA) of the in situ gel were identified. Central composite design (CCD) was adopted to optimize the formulation. MATERIALS AND METHODS: The ophthalmic in situ forming gels were prepared by cold method. Materials attributes were the amount of Poloxamer 407 and HPMC and CQA identified were Gel strength, mucoadhesive index, gelation temperature and % of drug release of both drug. RESULTS AND DISCUSSION: Optimized batch (F*) containing 16.75% poloxamer 407 and 0.54% HPMC K4M were exhibited all results in acceptable limits. Compared with the marketed formulation, optimized in situ gel showed delayed Tmax, improved Cmax and AUC in rabbit aqueous humor, suggesting the sustained drug release and better corneal penetration and absorption. CONCLUSION: According to the study, it could be concluded that DSP and TS would be successfully formulated as in situ gelling mucoadhesive system for the treatment of steroid responsive eye infections with the properties of sustained drug release, prolonged ocular retention and improved corneal penetration.

Current approaches for in vitro drug release study of long acting parenteral formulations.

Long acting parenteral formulations are preferred over conventional formulations for the treatment of chronic diseases. Prevalence of such diseases provoked the interest of researchers and pharmaceutical industries in the development of long acting parenteral formulations. The regulatory guidelines and pharmacopoeia have remained silent on dissolution methods for long acting parenteral formulations due to their diverse nature. The lack of compendial method for dissolution testing increases the duration of approval process for long acting parenteral formulations. This article reviews various dissolution methods used to study in vitro drug release profile of long acting parenteral formulations. Compendial as well as noncompendial methods, such as- rotating dialysis cell, dialysis tube, rotating bottle, shaking flask, single drop, inverted cup and incubation, are used by researchers for drug release profile of long acting parenteral formulations. This review article also highlights the advantages and disadvantages of reported dissolution methods along with the suitability of these methods for particular type of long acting formulation. The compiled work will help the researchers in designing the biorelevant dissolution method and expedite the development of long acting parenteral formulations.

Formulation and evaluation of clotrimazole transdermal spray.

CONTEXT: Transdermal spray (TS) of clotrimazole (CTZ) was formulated to improve the drug transport through the skin up to 12 h to achieve the antifungal efficacy. OBJECTIVE: The aim of present study was to formulate and evaluate antifungal transdermal spray to improve the permeation of clotrimazole across the skin and to decrease the dosing frequency in fungal infection. MATERIALS AND METHODS: Different ratios of ethanol and acetone and various grades of eudragit and ethyl cellulose were evaluated according to six criteria: viscosity, drying time, stickiness, appearance and integrity on skin and water washability. Propylene glycol (PG) and polyethylene glycol 400 (PEG 400) were used in the study as plasticizer and solubilizer. The TS was evaluated for in vitro drug release, spray angle, spray pattern, average weight per dose, pH, drug content, evaporation time, leak test and antifungal efficacy study. RESULTS AND DISCUSSION: Eudragit E100 and blend of ethanol and acetone (80:20) satisfied the desired criteria. The selection of optimized batch was based on the results of in vitro drug release, spray pattern and spray angle. The optimized batch showed the spray angle <85° and uniform spray pattern. The formulation containing PG showed higher drug release than PEG 400. The inclusion of eutectic mixture consisting of camphor and menthol (1:1) showed improved drug transport through the rat skin and larger mean zone of inhibition indicating the improved antifungal efficacy. CONCLUSION: The TS of CTZ can be an innovative and promising approach for the topical administration in the fungal diseases.

Exploration of statistical experimental design to improve entrapment efficiency of acyclovir in poly (d, l) lactide nanoparticles.

OBJECTIVE: In current exploration, systematic attempts have been made to improve the entrapment efficiency of a model hydrophilic drug substance, i.e. acyclovir, in poly (d, l) lactide (PLA) nanoparticles (NPs) using a modified nanoprecipitation technique. METHODS: Formulation parameters such as drug to polymer ratio, antisolvent selection, electrolyte (NaCl) addition, pH alteration and temperature were screened to improve the entrapment efficiency of acyclovir in PLA NPs. The temperature of the system (0-5 °C), phase volume ratio (1:2), stirring speed (2000 rpm), sonication time (5 min), etc. were kept constant during the preparation of NPs. Drug to polymer ratio and electrolyte addition emerged as critical formulation parameters affecting particle size as well as entrapment efficiency. Hence, in the present investigation a 3(2) full factorial design was used to investigate the combined influence of two factors, i.e. drug to polymer ratio (X1) and the amount of electrolyte, i.e. NaCl (X2) on particle size (Y1) and entrapment efficiency (Y2). The NPs were also evaluated for drug-excipient compatibility study by employing DSC and FT-IR analysis, whereas in vitro drug release studies were performed using dialysis bag technique in phosphate buffer pH 7.4. RESULTS: Statistically significant models were evolved to predict entrapment efficiency and particle size. The effect of factors X1, X2 and [Formula: see text] was found to be statistically significant in nature. Response variables, i.e. entrapment efficiency and particle size, were simultaneously optimized using desirability function using Design Expert software. This process allowed the selection of most suitable level of factors to achieve desired level of particle size and entrapment efficiency. The results of multiple linear regression analysis revealed that for obtaining desirable particle size (less than 250 nm) and entrapment efficiency (more than 17%), the NPs should be prepared using 1:3 drug to polymer ratio and 0.04 M NaCl. Acyclovir was found to be compatible with PLA as indicated by DSC and FT-IR studies. The experimental values obtained from the optimized formulation highly agreed with the predicted values. The drug release from the optimized formulation exhibited biphasic pattern and the drug release kinetics was best explained by Weibull model. CONCLUSION: In conclusion, results of the present study demonstrated that PLA NPs with expected particle size and entrapment efficiency can be obtained by adopting the concept of quality by design.

Serum GGT activity and hsCRP level in patients with type 2 diabetes mellitus with good and poor glycemic control: An evidence linking oxidative stress, inflammation and glycemic control.

BACKGROUND: Diabetes is undoubtedly one of the most challenging health problems in 21st century. Understanding the pathogenesis and preventing long term complications have been major goals of research in diabetes mellitus (DM). Research in the past few years has linked oxidative stress and inflammation to beta cell dysfunction. Aim of this study is to evaluate serum gamma-glutamyl transferase (GGT) activity (marker of oxidative stress) and high sensitivity C reactive protein (hsCRP) level (an inflammatory marker) in type 2 DM subjects with good and poor glycemic control. Further, we investigated correlation between serum GGT and hsCRP level with glycemic control (FBS, PP2BS, HbA1c) in subjects. METHODS: A cross sectional study consists of 150 patients out of them 50 patients having type 2 DM with good control (Group II), 50 patients with type 2 DM with poor control (Group III) and 50 normal healthy control (Group I) were selected. Serum GGT, serum hsCRP, FBS, PP2BS, HbA1c, and other biochemical investigations include serum liver enzymes and lipids were measured. RESULTS: Mean serum GGT and hsCRP concentration were statistically significantly higher in group III patients compared to group I and group II subjects as well as increased in group II compared to group I (p < 0.001). Further significant positive correlation was observed between GGT and hsCRP concentration as well as both with HbA1c, FBS, and PP2BS. CONCLUSIONS: Oxidative stress and inflammation appears to be a key component and also associated with poor glycemic control and further pathogenesis of diabetes and its complications. All our finding suggesting a link between oxidative stress, inflammation and glycemic control in patient with type 2 diabetes mellitus.

Microemulsion-based gel of terbinafine for the treatment of onychomycosis: optimization of formulation using D-optimal design.

The aim of the present investigation was to evaluate microemulsion as a vehicle for dermal drug delivery and to develop microemulsion-based gel of terbinafine for the treatment of onychomycosis. D-optimal mixture experimental design was adopted to optimize the amount of oil (X(1)), Smix (mixture of surfactant and cosurfactant; X(2)) and water (X(3)) in the microemulsion. The formulations were assessed for globule size (in nanometers; Y(1)) and solubility of drug in microemulsion (in milligrams per milliliter; Y(2)). The microemulsion containing 5.75% oil, 53.75% surfactant-cosurfactant mixture and 40.5% water was selected as the optimized batch. The globule size and solubility of the optimized batch were 18.14 nm and 43.71 mg/ml, respectively. Transmission electron microscopy showed that globules were spherical in shape. Drug containing microemulsion was converted into gel employing 0.75% w/w carbopol 934P. The optimized gel showed better penetration and retention in the human cadaver skin as compared to the commercial cream. The cumulative amount of terbinafine permeated after 12 h was 244.65 ± 18.43 µg cm(-2) which was three times more than the selected commercial cream. Terbinafine microemulsion in the gel form showed better activity against Candida albicans and Trichophyton rubrum than the commercial cream. It was concluded that drug-loaded gel could be a promising formulation for effective treatment of onychomycosis.

Microneedles: an emerging transdermal drug delivery system.

OBJECTIVES: One of the thrust areas in drug delivery research is transdermal drug delivery systems (TDDS) due to their characteristic advantages over oral and parenteral drug delivery systems. Researchers have focused their attention on the use of microneedles to overcome the barrier of the stratum corneum. Microneedles deliver the drug into the epidermis without disruption of nerve endings. Recent advances in the development of microneedles are discussed in this review for the benefit of young scientists and to promote research in the area. KEY FINDINGS: Microneedles are fabricated using a microelectromechanical system employing silicon, metals, polymers or polysaccharides. Solid coated microneedles can be used to pierce the superficial skin layer followed by delivery of the drug. Advances in microneedle research led to development of dissolvable/degradable and hollow microneedles to deliver drugs at a higher dose and to engineer drug release. Iontophoresis, sonophoresis and electrophoresis can be used to modify drug delivery when used in concern with hollow microneedles. Microneedles can be used to deliver macromolecules such as insulin, growth hormones, immunobiologicals, proteins and peptides. Microneedles containing 'cosmeceuticals' are currently available to treat acne, pigmentation, scars and wrinkles, as well as for skin tone improvement. SUMMARY: Literature survey and patents filled revealed that microneedle-based drug delivery system can be explored as a potential tool for the delivery of a variety of macromolecules that are not effectively delivered by conventional transdermal techniques.

Formulation development of ambroxol hydrochloride soft gel with application of statistical experimental design and response surface methodology.

The purpose of present work was to develop ambroxol hydrochloride soft gel formulation with the application of statistical experimental design and response surface methodology (RSM). A two-factor, three-level (3(2)) full factorial design of experiment with RSM was run to evaluate the main and interaction effect of two independent formulation variables that included the amount of low-acetylated gellan gum and sodium citrate. The dependent variables included viscosity (Y(1)), amount of drug release at 10 min (Y(2)) and 30 min (Y(3)), and gelation time (Y(4)). In order to obtain a formulation having the maximum amount of drug release at 10 min and minimum gelation time, RSM optimization was used. The prepared formulations were evaluated for pH, viscosity, rheological properties, gelation time, drug content, in vitro drug release, appearance, and taste. All the formulations showed a gelation time in the range of 6 to 48 min. The drug content in all the formulations was within limit (99.6 ± 1.56%). The viscosity of all the formulations was found in the range of 1872-12,182 cP. Dissolution studies of the formulations showed drug release in the range of 40.56-72.46% within 10 min and 80.2-100.5% within 30 min. Human evaluation tests revealed that all the gels possessed acceptable characteristics. This study showed that the soft gel formulation GA5, containing 0.3% of gellan gum and 0.4% of sodium citrate, has potential use as an immediate release soft gel for oral drug delivery. LAY ABSTRACT: The objective of this investigation was to develop a new, immediate-release, soft gel dosage form for ambroxol hydrochloride, an oral expectorant and mucolytic agent. This novel soft gel dosage form needs to be suitable for pediatric and geriatric patients as well as patients with dysphagia. A statistical technique was used for optimization of the gel formulation. The methodology, called a design of experiment with response surface methodology, evaluated several independent formulation variables, including the amount of two ingredients, low-acetylated gellan gum and sodium citrate. Their effects were studied by comparing physical properties of the gel such as viscosity, amount of drug release at 10 and 30 min, and gelation time. The final optimized formulation (0.3% of gellan gum and 0.4% of sodium citrate) was chosen to maximize the amount of drug release at 10 min, minimize gelation time, and optimize viscosity in a reasonable range. After this optimization exercise, the prepared ambroxol hydrochloride soft gel formulations were evaluated for pH, viscosity, rheological properties, gelation time, drug content, in vitro drug release, appearance, and taste. Human evaluation tests revealed that all the gels possessed acceptable organoleptic characteristics.

Development of directly compressible metformin hydrochloride by the spray-drying technique.

Metformin hydrochloride exhibits poor compressibility during compaction, often resulting in weak and unacceptable tablets with a high tendency to cap. The purpose of this study was to develop directly compressible metformin hydrochloride by the spray-drying technique in the presence of polymer. Metformin hydrochloride was dissolved in solutions containing a polymer, namely polyvinylpyrrolidone (PVP K30), in various concentrations ranging from 0-3% (m/V). These solutions were employed for spray-drying. Spray-dried drug was evaluated for yield, flow property and compressibility profile. Metformin hydrochloride spray-dried in the presence of 2% PVP K30 showed an excellent flow property and compressibility profile. From the calculated Heckel's parameter (Py = 2.086), it was demonstrated that the treated drug showed better particle arrangement in the initial compression stage. Kawakita analysis revealed better packability of the treated drug compared to the untreated drug. Differential scanning calorimetry and Fourier transform infrared spectroscopy experiments showed that the spray-dried drug did not undergo any chemical modifications. Tablets made from the spray-dried drug (90%, m/m) were evaluated for crushing strength, friability and disintegration time and the results were found satisfactory.