Current Drug Delivery - Volume 6, Issue 5, 2009

In the present study solid dispersions of Raloxifene HCl were prepared by melt mixing. As drug carriers, biodegradable/ biocompatible aliphatic polyesters were used. These formulations were compared to those based on extensively used drug carriers such as PEG and Gelucire 50/13. The used aliphatic polyesters namely poly(propylene succinate) (PPSu) and poly(propylene adipate) (PPAd) were prepared by melt polycondensation. The polyesters have melting points close to human body temperature and were used for first time as drug carries. Polymer cytocompatibility based on HUVEC cells viability in the presence of increasing concentrations of polymer was investigated and it was found that PPSu and PPAd exhibit comparable cytocompatibility with poly(dl-lactide). The physical state of solid dispersions was evaluated by FTIR, SEM and XRD techniques. In all cases the interactions between drug and carriers are limited and thus the dispersed drug was mainly in the crystalline state. SEM revealed that the particles size of the dispersed drug increases with increasing the drug amount. The release behavior of the drug is affected from both the drug amount and the kind of the used carrier. The drug is released almost immediately from PEG formulations while Gelucire results in sustained release. In formulations that polyesters were used as drug carriers the release is slower.

The present study performed by preparation and evaluation of floating tablets of Acyclovir as model drug for prolongation of gastric residence time. Floating effervescent tablets were formulated by various materials like hydroxypropyl methylcellulose K 4M, K 15M, psyllium husk, swelling agent as crospovidone and microcrystalline cellulose and gas generating agent like sodium bicarbonate and citric acid and evaluated for floating properties, swelling characteristics and in vitro drug release studies. Floating noneffervescent tablets were prepared by polypropylene foam powder and different matrix forming polymers like HPMC K 4M, Carbopol 934P, xanthan gum and sodium alginate. In vitro drug release studies were performed and drug release kinetics evaluated using the linear regression method was found to follow both the Higuchi and the Korsmeyer and Peppas equation. The drug release mechanism was found fickian type in most of the formulations.

The purpose of the present work was to formulate and evaluate skin permeability of a glipizide gel to assess its suitability for transdermal delivery. A polymer gel was prepared by soaking hydroxypropyl methyl cellulose (5 g) overnight in phosphate buffer: ethanol (50:50, v/v) and mixing it with separately prepared glipizide solution in the same vehicle to bring the concentration to 2 mg /ml. In vitro skin permeability was assessed in full thickness skin of rabbits and pigs. For in vivo studies New Zealand rabbits were used. In vitro passive permeation was carried out in Franz diffusion cell but for iontophoresis, diffusion cell was modified according to Glikfield design. Iontophoresis was performed at a current density of 0.5 mA/cm2 via silver/silver chloride electrodes with the passive controls but for in vivo study current density was reduced to 0.125mA/cm2. Blood samples were analyzed for drug content by HPLC and blood sugar levels were also recorded periodically during in vivo permeation. Results of the in vitro study indicated that iontophoresis considerably increased the permeation rate of glipizide compared to passive controls in both the skin types (P<0.05). For in vivo studies current densities and drug concentration had to be lowered to 0.125 mA/cm2 as excessive permeation resulting in hypoglycemic shocks were noted when study was carried out at a current density of 0.5 mA/cm2. The low intensity current was well tolerated. The plasma concentration of glipizide was significantly higher (P<0.05) than that obtained in the passive controls. The study indicated even at very low current density, iontophoresis could enhance the permeation of glipizide significantly.

The task of achieving efficient delivery of drugs that have poor bioavailability or narrow absorption windows have plagued the pharmaceutically industry for decades. Thus, much research has been dedicated to the development of novel polymeric-based gastroretentive drug delivery technologies that may optimize the bioavailability and subsequent therapeutic efficacy of such drugs. An effective approach of achieving this is through the prolongation of the gastric residence time employing several gastroretentive drug delivery mechanisms such as the use of buoyant systems, high density systems, magnetic systems, mucoadhesive systems, swelling/expanding systems, superporous hydrogels and the inclusion of gastric motility retarding agents with biocompatible polymeric materials. It is known that variations in the gastric physiology such as, gastric pH, and motility exhibit both intra-as well as inter-subject variability demonstrating a significant impact on the gastric retention time and drug delivery behavior. Nevertheless, gastroretentive drug delivery systems have shown promising results. Therefore, in this mini-review, current research and development in this field (i.e. over the last 3-5 years), the polymeric material used for the design of gastroretentive drug delivery systems and techniques employed for the pharmaceutical evaluation of gastroretentive technologies are comprehensively revealed and discussed in an assimilatory manner.

This study aimed at the preparation and characterization of preformed and in-situ formed liposomes for controlled delivery to the lungs. Two different liposome formulations were prepared and subjected to characterization of physical parameters (vesicle size, appearance, discharge rate, spray pattern and internal pressure) and drug release profile (% cumulative drug release and % drug retained). Formulations were then subjected to accelerated stability studies as per ICH guidelines. It was observed that vesicle size ranged between 2.35 ± 0.23 - 2.41± 0.3 μm and 1.22 ± 0.22- 1.34 ± 0.15 μm respectively for preformed and in-situ formed liposomes. The discharge rate and spray area were in ranges of 110 ± 2.4 -123 ± 2.6 & 115± 2.4 -127±2.3 mg/ actuation & 12.5 ±1.7 -14.1± 2.2 and 13.9 ± 2.1- 14.7± 2.0 cm2 respectively. In-situ liposomes showed better controlled release profile then preformed liposomes as it released 76.5± 2.4 - 58.5 ± 1.8 % drug in 12 hour while retaining 23.5 ± 1.9- 41.5 ± 1.6 % drug whereas preformed liposomes showed cumulative release of 66.5 ± 2.2- 84.5 ± 2.3 % and 15.5 ± 2.4- 33.5± 2.1 % fraction retained. Upon subjection to accelerated conditions for a period of 60 days, preformed liposome completely lost the objective of being controlled release formulation as they showed 92± 2.4 % cumulative release and only 08 ± 1.6 % fraction retained whereas in-situ formulation showed 62 ± 2.3 % cumulative release and 38 ± 2.1 % fraction retained.

The ultimate goal of any drug delivery system is the successful delivery of the drug to the body; however, patient compliance must not be overlooked. Fast dissolving drug delivery systems, such as, Mouth Dissolving Films (MDF), offer a convenient way of dosing medications, not only to special population groups with swallowing difficulties such as children and the elderly, but also to the general population. MDF are the novel dosage forms that disintegrate and dissolve within the oral cavity. Intra-oral absorption permits rapid onset of action and helps by-pass first-pass effects, thereby reducing the unit dose required to produce desired therapeutic effect. The present review provides an overview of various polymers that can be employed in the manufacture of MDF and highlights the effect of polymers and plasticizers on various physico-mechanical properties of MDF. It further gives a brief account of formulation of MDF and problems faced during its manufacture.

Metformin Hydrochloride (MF) is glucose lowering agent that is widely used for management for type II diabetes. MF is reported to be absorbed mainly in upper part of GIT. It is having narrow absorption window and high water solubility, and it would be more beneficial to retain the drug in stomach for prolonged duration so as to achieve maximum absorption and better bioavailability. A conventional oral CR formulation releases most of the drug content at the colon, which requires that the drug will be absorbed from the colon. The present investigation is aimed to develop novel gastroretentive (GR) drug delivery system, which releases the drug in the absorption window. As well to provide controlled release drug profile that can result patient compliance and therapeutic success. Floating tablets of MF was prepared using sodium alginate, and sodium carboxymethylcellulose as a gelling agent, and release modifier, respectively. Eudragit NE 30 D was used as sustained release polymer to control the initial burst release. Drug and excipients compatibility studies were monitored by thermal analysis using differential scanning calorimeter. 32 full factorial design was applied to optimize the formulation. The DSC thermogram of drug, polymer and physical mixtures revealed that there was no known interaction between drug and polymers. The prepared tablets were evaluated for in vitro dissolution, in vitro buoyancy, percentage swelling, percentage erosion and similarity factors with marketed tablets. The optimization study using a 32 full factorial design revealed that the amount of sodium alginate and sodium carboxymethylcellulose had a significant effect on t50, t90, Flag and f2. Thus, by selecting a suitable composition of release rate modifier and gel forming agent, gastroretentive system can be developed with the desired dissolution profile. This study indicated that the MF GR tablets prepared using sodium alginate and sodium carboxymethylcellulose can successfully employed as a once-a-day oral controlled release drug delivery system.

The aim of the present investigation was to prepare and optimize the formulation of mouth dissolving film of salbutamol sulphate by applying experimental design technique. The films were prepared using hydroxypropyl methylcellulose, polyvinyl pyrrolidone and polyvinyl alcohol by solvent evaporation technique. Simplex lattice design and desirability function were adopted for the preparation of film possessing desirable and optimized characteristics. Tensile strength, elastic modulus, percentage strain, load at yield, and percentage drug release were selected as dependent variables. Regression equations and contour plots were used to relate the dependent and independent variables. The concept of similarity factor Sd was used to prove similarity of dissolution between distilled water and simulated saliva (pH = 6.8). The polymers greatly influenced the mechanical properties and % drug release from the film. From the computed value of desirability function, it was determined that the film containing hydroxypropyl methylcellulose and polyvinyl alcohol was the best batch. The experimental design serves to be a useful tool for the formulation development of mouth dissolving film.

Phase-sensitive in situ gel forming controlled release formulations of cyclosporine were prepared using poly (lactide-co-glycolide) and a solvent system consisting of various proportions of benzyl benzoate and benzyl alcohol. Uniformity of content of cyclosporine in the formulation and in vitro release samples was determined by radio immune assay (RIA). FTIR and CD spectroscopy ratified the conformational stability of cyclosporine in the formulation and in vitro release samples, respectively. Rheological properties of the formulations, assessed under isothermal conditions, showed dilatant behavior of all the formulations. In vivo studies were carried out on the optimized formulations vis-a-vis pure cyclosporine in rats and drug levels were monitored for 13 days. Mean plasma concentration of cyclosporine was calculated for all the animals and pharmacokinetic parameters were determined using Win NonLin software. The studies construed better regulation of plasma drug levels with the optimized formulation vis-à-vis routine once-a-day administration of cyclosporine. The subcutaneous tissues, further subjected to histopathological examinations ascertained the biocompatibility of the formulation.

The objective of the present study is to develop Superporous Hydrogel (SPH) and SPH composites (SPHC) as pH-sensitive drug delivery system for Pantaprazole sodium. In this investigation, Superporous hydrogels containing poly(methacrylic acid-co-acrylamide) with interconnected pores of several hundreds of micrometer were prepared using radical polymerization of methacrylic acid and acrylamide in the presence of N,N-methylene-bis-acrylamide as crosslinking agent. A gas blowing method using bicarbonate as a foaming agent was applied to introduce the porous structure. SPH composite polymers were made in the same way, except for using Ac-Di-Sol as a stabilizer. The structures of the SPH and SPH composites were characterized by FT-IR and Scanning electron microscopy (SEM). Apparent density and swelling ratio studies were also carried out. The swelling properties and mechanical strength of SPHs were affected by the addition of the mechanical stabilizer, Ac-Di-Sol. Results indicated that SPH polymers have more pores and higher swelling ratio but less mechanical stability compared to SPH composite polymers, which have less pores and lower swelling ratio but a higher mechanical stability. With a change in pH from acidic to basic, a considerable increase in swelling was observed for all the formulations. Since the prepared SPH and SPHC swell only in the basic pH, it may be concluded that SPH and SPHC can be used as pH-sensitive drug delivery systems for Pantoprazole sodium.

Objective: The main objective of the present study was to establish and evaluate matrix type transdermal therapeutic systems containing new polymeric combinations (Eudragit E PO/Eudragit RL 100 & Plasdone S 630) as polymers and Labetalol Hydrochloride (LBHCl) as a model drug. Experimental: The matrix type TTS of LBHCl were prepared by film casting technique. The patches were characterized for physical, in vitro release studies and ex-vivo permeation studies using human cadaver skin. On the basis of in vitro drug release study and skin permeation, formulation A1 was found more effective than the other formulations, so it was selected as the optimized formulation. The optimized formulation patch was assessed in detail for its pharmacokinetic, pharmacodynamic, skin irritation potential, and stability studies. Results: The maximum percentage drug release and Permeation in 48 hrs were 92.43 % and 76.24 % respectively for optimized patch. The Korsmeyer peppas release exponent value of 0.604 in the optimized formulation was highly suggestive of release mechanism towards first order release. The observations obtained from the in vivo characterization of the optimized patch were indicative of sustained action of the developed formulation. The interaction studies analysis indicated no chemical interaction among the drug and polymers. The optimized patch appeared free from potentially hazardous skin irritation as observed by skin irritation score of 0.915<2.00 (under Draize score test). The optimized formulation was found to be stable at ambient storage conditions. Conclusion: The above TTS holds promise for improved bioavailability and better management of hypertension in long term basis.

One of the factors responsible for the poor immunogenicity of synthetic peptide antigens is the lack of conformational integrity. Embedding the minimal epitopes in helix-promoting peptide sequences has successfully enhanced the immunogenicity of the epitopes derived from the α-helical regions of the M protein of group A streptococci (Streptococcus pyogenes, GAS). However, the introduction of “foreign” peptide sequences is believed to have an unfavourable impact on the antigen specificity. In the current study, we employed a non-peptide approach, using topological carbohydrate templates, to induce helical conformation of the peptide antigens. Utilized together with the advances of the lipid core peptide system and chemoselective ligation, five GAS vaccine candidates incorporating the minimal epitope J14i (ASREAKKQVEKALE) were synthesized with high purity. Circular dichroism studies indicated that the template-assembled peptides formed α-helix bundles. This atom-economic strategy also reduces the complexity and cost of vaccine production by simply reducing the peptide epitope size.