In situ forming phase-inversion implants for sustained ocular delivery of triamcinolone acetonide.

The objectives of this study were to develop biodegradable poly-lactic-co-glycolic acid (PLGA) based injectable phase inversion in situ forming system for sustained delivery of triamcinolone acetonide (TA) and to conduct physicochemical characterisation including in vitro drug release of the prepared formulations. TA (at 0.5%, 1% and 2.5% w/w loading) was dissolved in N-methyl-2-pyrrolidone (NMP) solvent and then incorporated 30% w/w PLGA (50/50 and 75/25) polymer to prepare homogenous injectable solution. The formulations were evaluated for rheological behaviour using rheometer, syringeability by texture analyser, water uptake and rate of implant formation by optical coherence tomography (OCT) microscope. Phase inversion in situ forming formulations were injected into PBS pH 7.3 to form an implant and release samples were collected and analysed for drug content using a HPLC method. All formulations exhibited good syringeability and rheological properties (viscosity: 0.19-3.06 Pa.s) by showing shear thinning behaviour which enable them to remain as free-flowing solution for ease administration. The results from OCT microscope demonstrated that thickness of the implants were increased with the increase in time and the rate of implant formation indicated the fast phase inversion. The drug release from implants was sustained over a period of 42 days. The research findings demonstrated that PLGA/NMP-based phase inversion in situ forming implants can improve compliance in patient's suffering from ocular diseases by sustaining the drug release for a prolonged period of time and thereby reducing the frequency of ocular injections.

Investigation on solution-to-gel characteristic of thermosensitive and mucoadhesive biopolymers for the development of moxifloxacin-loaded sustained release periodontal in situ gels.

The objectives of present research were to develop and characterize thermosensitive and mucoadhesive polymer-based sustained release moxifloxacin in situ gels for the treatment of periodontal diseases. Poloxamer- and chitosan-based in situ gels are in liquid form at room temperature and transform into gel once administered into periodontal pocket due to raise in temperature to 37 °C. Besides solution-to-gel characteristic of polymers, their mucoadhesive nature aids the gel to adhere to mucosa in periodontal pocket for prolonged time and releases the drug in sustained manner. These formulations were prepared using cold method and evaluated for pH, solution-gel temperature, syringeability and viscosity. In vitro drug release studies were conducted using dialysis membrane at 37 °C and 50 rpm. Antimicrobial studies carried out against Aggregatibacter actinomycetemcomitans (A.A.) and Streptococcus mutans (S. Mutans) using agar cup-plate method. The prepared formulations were clear and pH was at 7.01-7.40. The viscosity of formulations was found to be satisfactory. Among the all, formulations comprising of 21% poloxamer 407 and 2% poloxamer 188 (P5) and in combination with 0.5% HPMC (P6) as well as 2% chitosan and 70% ß-glycerophosphate (C6) demonstrated an ideal gelation temperature (33-37 °C) and sustained the drug release for 8 h. Formulations P6 and C6 showed promising antimicrobial efficacy with zone of inhibition of 27 mm for A.A. and 55 mm for S. Mutans. The developed sustained release in situ gel formulations could enhance patient's compliance by reducing the dosing frequency and also act as an alternative treatment to curb periodontitis.

Lipid based nanocarriers system for topical delivery of photosensitizers.

Topical photodynamic therapy (PDT) is a non-invasive technique used in the treatment of malignant and non-malignant skin diseases. It offers great promise because of its simplicity, enhanced patient compliance, localisation of the photosensitizer, as well as the use of light and oxygen to achieve photocytotoxicity. Despite progress in photosensitizer-mediated topical PDT, its clinical application is limited by poor penetration of photosensitizers through the skin. Therefore, much effort has been made to develop nanocarriers that can tackle the challenges of conventional photosensitizer-mediated PDT for topical delivery. This review discusses recent data on the use of different types of lipid-based nanocarriers in delivering photosensitizer for topical PDT.

Application of diverse natural polymers in the design of oral gels for the treatment of periodontal diseases.

The objective of this study was to prepare periodontal gels using natural polymers such as badam gum, karaya gum and chitosan. These gels were tested for their physical and biochemical properties and assessed for their antibacterial activity against Aggregatibacter actinomycetemcomitans and Streptococcus mutans, two pathogens associated with periodontal disease. Badam gum, karaya gum and chitosan were used to prepare gels of varying concentrations. Moxifloxacin hydrochloride, a known antimicrobial drug was choosen in the present study and it was added to the above gels. The gels were then run through a battery of tests in order to determine their physical properties such as pH and viscosity. Diffusion studies were carried out on the gels containing the drug. Antimicrobial testing of the gels against various bacteria was then carried out to determine the effectiveness of the gels against these pathogens. The results showed that natural polymers can be used to produce gels. These gels do not have inherent antimicrobial properties against A. actinomycetemcomitans and S. mutans. However, they can be used as a transport vehicle to carry and release antimicrobial drugs.

Recent Advances in Non-Invasive Delivery of Macromolecules using Nanoparticulate Carriers System.

BACKGROUND: The drug delivery of macromolecules such as proteins and peptides has become an important area of research and represents the fastest expanding share of the market for human medicines. The most common method for delivering macromolecules is parenterally. However parenteral administration of some therapeutic macromolecules has not been effective because of their rapid clearance from the body. As a result, most macromolecules are only therapeutically useful after multiple injections, which causes poor compliance and systemic side effects. METHOD: Therefore, there is a need to improve delivery of therapeutic macromolecules to enable non-invasive delivery routes, less frequent dosing through controlled-release drug delivery, and improved drug targeting to increase efficacy and reduce side effects. RESULT: Non-invasive administration routes such as intranasal, pulmonary, transdermal, ocular and oral delivery have been attempted intensively by formulating macromolecules into nanoparticulate carriers system such as polymeric and lipidic nanoparticles. CONCLUSION: This review discusses barriers to drug delivery and current formulation technologies to overcome the unfavorable properties of macromolecules via non-invasive delivery (mainly intranasal, pulmonary, transdermal oral and ocular) with a focus on nanoparticulate carrier systems. This review also provided a summary and discussion of recent data on non-invasive delivery of macromolecules using nanoparticulate formulations.

IDENTIFICATION OF PHARMACEUTICAL EXCIPIENT BEHAVIOR OF CHICKPEA (CICER ARIETINUM) STARCH IN GLICLAZIDE IMMEDIATE RELEASE TABLETS.

In the past few years, there are number of researchers carrying out their research on the excipients derived from polysaccharides and some of these researches show that natural excipients are comparable and can serve as an alternative to the synthetic excipients. Hence, the objectives of this research are to characterize the naturally sourced chickpea starch powder and to study the pharmaceutical excipient behavior of chickpea starch in gliclazide immediate release (IR) tablets. In this research, the binding properties of chickpea starch were compared to that of povidone, whereas the disintegrant properties of chickpea starch were compared to those of crospovidone, croscarmellose sodium and sodium starch glycolate. Flow property of chickpea starch was assessed with the measurement of bulk density, tapped density, compressibility index and angle of repose. Calibration curve for gliclazide in phosphate buffer pH 7.4 was developed. Gliclazide IR tablets were then produced with direct compression method. Physicochemical characteristics of the tablets, including thickness, tablet weight uniformity, hardness, disintegration time and friability were evaluated. Then, in vitro dissolution studies were performed by following United States Pharmacopeia (USP) dissolution method. The dissolution results were analyzed and compared with t30, t50, dissolution efficiency (DE). Lastly, drug-excipient compatibility studies, including Fourier transform infrared (FTIR) spectroscopic analysis and differential scanning calorimetric (DSC) analysis were carried out. Fair flow property was observed in the chickpea starch powder. Furthermore, the tablets produced passed all the tests in physicochemical characteristics evaluation except hardness and disintegration test. Additionally, in vitro dissolution studies show that chickpea starch acted as a disintegrant instead of a binder in gliclazide IR tablets and its disintegrant properties were comparable to those of crospovidone, croscarmellose sodium and sodium starch glycolate. Besides that, gliclazide was also compatible with the excipients used. Chickpea starch acted as a disintegrant in gliclazide IR tablets, instead of a binder. Therefore, chickpea starch can be a promising disintegrant in gliclazide IR tablets.

Formulation of Gastric Floating System Using Bio-Sourced Terminalia Catappa Gum and in vivo Evaluation.

A central composite design was applied to design a novel gastric floating drug delivery system comprising propranolol HCl in Terminalia catappa gum and to evaluate the buoyancy, in vitro drug release behavior, and pharmacokinetic parameters. All formulations exhibited good buoyancy properties in vitro reflected by floating lag time of 1-110 sec, total floating time of 9-16 h and prolonged release behaviour (upto 12 h). Statistically optimised formulation (PBGRso) was orally administered to human volunteers under both fasted and fed conditions to evaluate gastric floating behavior under different food conditions by X-ray evaluation. In vivo studies of optimised formulations revealed that the gastric residence time of floating tablets was enhanced in the fed but not in the fasted state. Pharmacokinetic studies of the optimised Terminalia catappa formulation and a commercial product (Ciplar LA 80) carried out on healthy human volunteers showed a significant improvement in the bioavailability (132%) of propranolol HCl released from from the experimental Terminalia catappa formulations compared with Ciplar LA 80.

Formulation and optimization of gastric floating drug delivery system using Central composite design and its biopharmaceutical evaluation.

The present work investigates the formulation and biopharmaceutical estimation of gastric floating drug delivery system (GFDDS) of propranolol HCl using semi-synthetic polymer carboxymethyl ethyl cellulose (CMEC) and a synthetic polymer polyethylene oxide (PEO). A central composite design was applied for optimization of polymer quantity (CMEC or PEO) and sodium bicarbonate concentration as independent variables. The dependent variables evaluated were: % of drug release at 1 hr (D1hr), % drug release at 3 hr (D3hr) and time taken for 95% of drug release (t95). Numerical optimization and graphical optimization were conducted to optimize the response variables. All observed responses of statistically optimized formulations were in high treaty with predicted values. Accelerated stability studies were conducted on the optimized formulations at 40 ± 2°C/75% ± 5% RH and confirm that formulations were stable. Optimized formulations were evaluated for in vivo buoyancy characterization in human volunteers and were found buoyant in gastric fluid. Gastric residence time was enhanced in the fed but not the fasted state. The optimized formulations and marketed formulation were administered to healthy human volunteers and evaluated for pharmacokinetic parameters. Mean residence time (MRT) was prolonged and AUC levels were increased for both optimized floating tablets when compared with marketed product. High relative bioavailability obtained with optimized gastric floating tablets compared to commercial formulation, indicated the improvement of bioavailability.

Preparation and in vitro characterization of a non-effervescent floating drug delivery system for poorly soluble drug, glipizide.

The aim of the present study was to formulate a non-effervescent floating drug delivery system of glipizide, a poorly water soluble drug. The solubility of glipizide was initially enhanced using a solid dispersion (SD) strategy with the help of hydrophilic carriers such as poloxamer, cyclodextrin, and povidone. The optimized core material/SD was further formulated into non-effervescent floating tablets (NEFT) by using matrix ballooning inducers, such as crospovidone and release retarding agents including HPMC and PEO. Poloxamer-based solid dispersions prepared by a solvent evaporation technique showed the highest dissolution rate (1 : 10 drug to carrier ratio) compared with all other dispersions. NEFT were evaluated for all physico-chemical properties including in vitro buoyancy, dissolution, and release rate. All of the tablets were found to be within pharmacopoeial limits and all of the formulations exhibited good floating behavior. The formulations (F2 and F3) were optimized based on their 12 h drug retardation with continuous buoyancy. The optimized formulations were characterized using FTIR and DSC and no drug and excipient interaction was found. In-vitro buoyancy and dissolution studies showed that non-effervescent floating drug delivery systems provide a promising method of achieving prolonged gastric retention time and improved bioavailability of glipizide.

Formulation of gastroretentive floating drug delivery system using hydrophilic polymers and its in vitro characterization

The aim of the present research is to formulate and evaluate the gastroretentive floating drug delivery system of antihypertensive drug, propranolol HCl. Gastroretentive floating tablets (GRFT) were prepared by using a synthetic hydrophilic polymer polyethylene oxide of different grades such as PEO WSR N-12 K and PEO 18 NF as release retarding polymers and calcium carbonate as gas generating agent. The GRFT were compressed by direct compression strategy and the tablets were evaluated for physico-chemical properties, in vitro buoyancy, swelling studies, in vitro dissolution studies and release mechanism studies. From the dissolution and buoyancy studies, F 9 was selected as an optimized formulation. The optimized formulation followed zero order rate kinetics with non-Fickian diffusion mechanism. The optimized formulation was characterised with FTIR studies and observed no interaction between the drug and the polymers.

O objetivo da presente pesquisa é o de formular e avaliar o sistema de liberação de fármaco gastrorretentivo flutuante, contendo o anti-hipertensivo, cloridrato de propranolol. Comprimidos gastrorretentivo flutuantes (GRFT) foram preparados utilizando um polímero hidrofílico sintético, o óxido de polietileno, de diferentes graus, tais como GE WSR N-12 K e GE 18 NF, como polímeros de retardamento de liberação, e carbonato de cálcio, como agente gerador de gases. Os GRFT foram comprimidos por compressão direta e avaliados para determinação das propriedades físico-químicas, flutuabilidade in vitro, estudos de inchamento, de dissolução in vitro e de mecanismo de liberação. Dos testes de dissolução e de flutuabilidade, selecionou-se F 9 como formulação otimizada. A formulação otimizada seguiu cinética de ordem zero, com mecanismo de difusão não-Fickiano. Essa formulação foi caracterizada por estudos de FTIR, não se observando interação entre o fármaco e os polímeros.

An in vitro and in vivo investigation into the suitability of compression coated tablets of indomethacin for the treatment of rheumatoid arthritis which follow circadian rhythms.

OBJECTIVE: The aim of this study was to develop chronotherapeutic drug delivery system of indomethacin using polyethylene oxide (PEO) with a predetermined lag time of 6 h by compression coating technique. MATERIALS AND METHODS: Solid dispersions (SD) of indomethacin were prepared using novel carrier sucrose fatty acid ester (SFE 1815) to increase the in vitro dissolution. The optimized SD was formulated as immediate release core tablet which were further coated with PEO (WSR Coagulant or WSR N12 K) using compression coating technique. Compression coated tablets formulated with PEO WSR Coagulant in 1:1.7 ratio of core tablet weight and coating polymer was considered as optimized formulation, which was further characterized by differential scanning calorimetry, X-ray diffractometry, Fourier transformed infrared spectroscopy, and scanning electron microscopy. RESULTS: The results indicated that there was no chemical incompatibility and slight change in surface properties. C(max), area under the curve (AUC(0-t)), and T(max) following oral ingestion of commercial capsule (Indocap) and optimized formulation (CT 4) were found to be 1973.18 ± 36.89 ng/mL, 11090.09 ± 131.21 ng/mL/h, 0.99 ± 0.02 h and 2115.46 ±6 2.61, 10413.14 ± 299.66 ng/mL/h, 7.00±0.02 h, respectively. CONCLUSION: Unaltered AUC(0-t) and C(max), but delayed T(max) indicated clear lag time before immediate release of drug which is suitable for treating rheumatoid arthritis following circadian rhythm.

Design and evaluation of a gastroretentive drug delivery system for metformin HCl using synthetic and semi-synthetic polymers.

The aim of the present research was to prepare and evaluate a gastroretentive drug delivery system for metformin HCl, using synthetic and semi-synthetic polymers. The floating approach was applied for preparing gastroretentive tablets (GRT) and these tablets were manufactured by the direct compression method. The drug delivery system comprises of synthetic and semi-synthetic polymers such as polyethylene oxide and Carboxymethyl ethyl cellulose (CMEC) as release-retarding polymers. GRT were evaluated for physico-chemical properties like weight variation, hardness, assay friability, in vitro floating behaviour, swelling studies, in vitro dissolution studies and rate order kinetics. Based upon the drug release and floating properties, two formulations (MP04 & MC03) were selected as optimized formulations. The optimized formulations MP04 and MC03 followed zero order rate kinetics, with non-Fickian diffusion and first order rate kinetics with erosion mechanism, respectively. The optimized formulation was characterised with FTIR studies and it was observed that there was no interaction between the drug and polymers.

Thermal sintering: a novel technique in the design of gastroretentive floating tablets of propranolol HCl and its evaluation.

The aim of the present investigation was to formulate thermally sintered floating tablets of propranolol HCl, and to study the effect of sintering conditions on drug release, as well as their in vitro buoyancy properties. A hydrophilic polymer, polyethylene oxide, was selected as a sintered polymer to retard the drug release. The formulations were prepared by a direct compression method and were evaluated by in vitro dissolution studies. The results showed that sintering temperature and time of exposure greatly influenced the buoyancy, as well as the dissolution properties. As the sintering temperature and time of exposure increased, floating lag time was found to be decreased, total floating time was increased and drug release was retarded. An optimized sintered formulation (sintering temperature 50 degrees C and time of exposure 4 h) was selected, based on their drug retarding properties. The optimized formulation was characterized with FTIR and DSC studies and no interaction was found between the drug and the polymer used.

Characterization and in vitro drug release studies of a natural polysaccharide Terminalia catappa gum (Badam gum).

The main objective of the present study is the physicochemical characterization of naturally available Terminalia catappa gum (Badam gum [BG]) as a novel pharmaceutical excipient and its suitability in the development of gastroretentive floating drug delivery systems (GRFDDS) to retard the drug for 12 h when the dosage form is exposed to gastrointestinal fluids in the gastric environment. As BG was being explored for the first time for its pharmaceutical application, physicochemical, microbiological, rheological, and stability studies were carried out on this gum. In the present investigation, the physicochemical properties, such as micromeritic, rheological, melting point, moisture content, pH, swelling index, water absorption, and volatile acidity, were evaluated. The gum was characterized by scanning electron microscopy, differential scanning calorimetry (DSC), powder X-ray diffraction studies (PXRD), and Fourier transform infrared spectroscopy (FTIR). Gastroretentive floating tablets of BG were prepared with the model drug propranolol HCl by direct compression methods. The prepared tablets were evaluated for all their physicochemical properties, in vitro buoyancy, in vitro drug release, and rate order kinetics. PBG 04 was selected as an optimized formulation based on its 12-h drug release and good buoyancy characteristics. The optimized formulation was characterized with FTIR, DSC, and PXRD studies, and no interaction between the drug and BG was found. Thus, the study confirmed that BG might be used in the gastroretentive drug delivery system as a release-retarding polymer.

Design and in vitro evaluation of effervescent gastric floating drug delivery systems of propanolol HCl.

Abstract. The purpose of this research was to develop and evaluate effervescent gastric floating tablets of propranolol HCl. The oral delivery of antihypertensive propranolol HCl was facilitated by preparing an effervescent floating dosage form which could increase its absorption in the stomach by increasing the drug's gastric residence time. In the present work, effervescent floating tablets were prepared with a hydrophilic carrier such as polyethylene oxide (PEO WSR N 60K and PEO WSR 303) as a release retarding agent and sodium bicarbonate as a gas generating agent. The prepared tablets were evaluated for all their physicochemical properties, in vitro buoyancy, drug release and rate order kinetics. From the results, P9 was selected as an optimized formulation based on their 12 h drug release, minimal floating lag time and maximum total floating time. The optimized formulation followed first order rate kinetics with erosion mechanism. The optimized formulation was characterized with FTIR studies and no interaction between the drug and the polymers were observed.

Statistical optimization of a novel excipient (CMEC) based gastro retentive floating tablets of propranolol HCl and it's in vivo buoyancy characterization in healthy human volunteers.

The objective of the present investigation is to formulate gastro retentive floating drug delivery systems (GRFDDS) of propranolol HCl by central composite design and to study the effect of formulation variables on floating lag time, D1hr (% drug release at 1 hr) and t90 (time required to release 90% of the drug). 3 factor central composite design was employed for the development of GRFDDS containing novel semi synthetic polymer carboxymethyl ethyl cellulose (CMEC) as a release retarding polymer. CMEC, sodium bicarbonate and Povidone concentrations were included as independent variables. The tablets were prepared by direct compression method and were evaluated for in vitro buoyancy and dissolution studies. From the polynomial model fitting statistical analysis, it was confirmed that the response floating lag time and D1hr is suggested to quadratic model and t90 is suggested to linear model. All the statistical formulations followed first order rate kinetics with non-Fickian diffusion mechanism. The desirability function was used to optimize the response variables, each having a different target, and the observed responses were highly agreed with experimental values. Statistically optimized formulation was characterized by FTIR and DSC studies and found no interactions between drug and polymer. The results demonstrate the feasibility of the model in the development of GRFDDS containing a propranolol HCl. Statistically optimized formulation was evaluated for in vivo buoyancy studies in healthy humans for both fed and fasted states. From the results, it was concluded that gastric residence time of the floating tablets were enhanced at fed stage but not in fasted state.