With the discovery of insulin in 1922, identification and commercialization of potential protein and peptide drugs have been increased. Since then, research and development to improve the means of delivering protein therapeutics to patients has begun. The research efforts have followed two basic pathways: One path focused on noninvasive means of delivering proteins to the body and the second path has been primarily aimed at increasing the biological half-life of the therapeutic molecules. The search for approaches that provide formulations that are stable, bioavailable, readily manufacturable, and acceptable to the patient, has led to major advances in the development of nasal and controlled release technology, applicable to every protein or peptide. In several limited cases, sustained delivery of peptides and proteins has employed the use of polymeric carriers. More successes have been achieved by chemical modification using amino acid substitutions, protein pegylation or glycosylation to improve the pharmacodynamic properties of certain macromolecules and various delivery systems have been developed like the prolease technology, nano-particulate and microparticulate delivery systems, and the mucoadhesive delivery of peptides. The needle and syringe remain the primary means of protein delivery. Major hurdles remain in order to overcome the combined natural barriers of drug permeability, drug stability, pharmacokinetics, and pharmacodynamics of protein therapeutics. In our present review we have tried to compile some recent advances in protein and peptide drug delivery systems.

The biopharmaceutical classification system (BCS) is a new concept in the field of pharmaceutical science and technology. This is a valuable tool for the formulation scientists, for the selection and design of the formulation of any drug substance. The recent developments have also enabled us to predict the solubility and permeability characteristics of the drug molecule in the early development stages so that the necessary structural changes can be made to the molecule in order to optimize the pharmacokinetic parameters. The BCS has also got a place in various guidance documents of regulatory importance. This article reviews the criteria for classifying drugs according to the BCS and discusses further potential applications of the BCS, including the developments of new drugs and controlled release products.

Glass transition temperature (Tg) is an important tool used to modify physical properties of drug and polymer molecules. Tg is shown by certain crystalline as well as amorphous solids. During the process of heating, some solid gets melted and if quench cooled, instead of crystallizing, gets converted to amorphous solid form appearing as that of glass. This glass formation is seen because of the dynamic arrest of molecules forming a disordered state at Tg. The molecules/atoms in glassy state are subject to only vibration and not translational and rotational motion. Mainly, at Tg, conversion of glassy (vitrified, amorphous) solid to rubbery (viscous liquid) takes place. Numerous factors like structural change in molecules, cooling rate and incorporation of additives alter the Tg. Techniques like differential scanning calorimetry, elastic modulus, broad-line NMR are used to measure the Tg of substances. The change in Tg has been carried out to improve dissolution and bioavailability, processing and handling qualities of the material.

The development of formulations for anti-cancer drugs imposes challenges owing to the different physicochemical attributes of the compounds as well as the need to deliver the compound to the desired target and/or tumor sites. In this article we present case studies to discuss recent formulation related work for both paclitaxel and topotecan. As enumerated by the case studies, biopharmaceutical and pharmacokinetic challenges are imposed in design and optimization of suitable dosage forms for both intravenous and oral drug delivery. The focus is on selection of excipients which may play additional role(s) in contributing towards the disposition of both paclitaxel and topotecan.

Aim of this paper is to develop and evaluate a physiologically activated in situ gel for local periodontal application. The gel, when at formulation pH and temperature (pH 6, 25°C) will be at liquid form which will be converted to gel at body pH and temperature (pH 7.4, 37°C) showing ease of administration and prolonged duration of action. Chitosan which was both mucoadhesive as well as pH simulative polymer was used in combination with pluronic F-127 which is a temperature simulated gelation polymer. Prilocaine hydrochloride was used as model drug to check the efficacy of the developed in-situ gel system. Different combination of Chitosan and pluronic F-127 were tested and final combination of 0.5% w/v and 10% w/v of Chitosan and pluronic F-127 respectively were selected and further evaluated for parameters like physicochemical properties, viscosity, gelation pH, gelation temperature, in-vitro release, sterility testing and stability testing. The system thus developed was found to be clear and have good viscosity with prolonged release at pH 7.4 and 37°C. The formulation can be easily packaged and sterilized with method employed. As per ICH guidelines gel was found to be stable and a shelf life of 2 years was assigned to the formulation.

The present study deals with the formulation of fast dissolving tablets of poorly soluble carbamazepine by the direct compression technique with β -cyclodextrin complexes using various super disintegrants like Indion-414, croscarmellose sodium, crospovidone and sodium starch glycolate. Carbamazepine is used to control different types of seizures in the treatment of epilepsy. Poor solubility in biological fluids is the major problem with this drug as also its poor bioavailability after oral administration. The rate of absorption and/or the extent of bioavailability for such a poor soluble drug is controlled by rate of dissolution in gastrointestinal fluids. Hence, to enhance the solubility of the drug, a complex of carbamazepine was prepared with β -cyclodextrin and this complex was compressed into tablets. The prepared tablets were evaluated for hardness, friability, drug content, weight variation, disintegrating time, wetting time, in vitro dissolution studies, etc. The prepared tablets were characterized by DSC, Fourier transform infrared spectroscopy (FTIR) and stability studies. The different formulations showed disintegration times between the ranges of 26.86 and 58.54 s. Drug release showed time between the ranges of 4 and 12min. Among all the formulations, B8 showed 99.89% drug release within 4min. Thus, B8 was considered as the best among the other formulations. No chemical interaction between the drug and the excipients was confirmed by DSC and FTIR studies. The stability study was conducted as per the ICH guidelines and the formulations were found to be stable, with insignificant changes in hardness, drug content and disintegration time. These results revealed that fast dissolving tablets of the poorly soluble drug, carbamazepine, showing enhanced dissolution and, hence, better patient compliance.

The purpose of the present investigation was to design a formulation of orodispersible tablets of Etoricoxib by adopting a systematic approach of 3 ² factorial design and to evaluate various quality control parameters. Etoricoxib is a novel, selective second-generation cyclooxygenase-2 inhibitor administered orally as an analgesic and antiinflammatory drug that is used for the treatment of osteoarthritis, rheumatoid arthritis and gouty arthritis. The poor aqueous solubility of the drug leads to variable dissolution rates. In the present investigation, an attempt has been made to prepare orodispersible tablets of Etoricoxib using three different directly compressible fillers to improve mouthfeel with an enhanced dissolution rate. In the study, a 3 ² full factorial design was adopted to investigate the joint influence of two formulation variables: amount of mannitol and crospovidone and the evaluation thereof. Response surface plots were also presented to represent graphically the effect of the independent variables on the disintegration time and drug percent dissolved in 60 s. The statistical model is mathematically valid as the experimental (actual) values and predicted values suggested by the full model were relatively close to each other. This systematic formulation approach will help in understanding the effect of formulation variables and permits the arbitrary selection of a batch of tablets with improved dissolution profile after oral administration of the selective COX-2 inhibitor.

Tetracycline is a broad spectrum antimicrobial agent, which is formulated into films and evaluated for the treatment of periodontitis. Chitosan films containing tetracycline in three different concentrations (10, 20, and 30% w/w to the weight of polymer) were prepared by the solution casting method, using 1% v/v acetic acid solution. The prepared films were evaluated for various properties such as weight variation, tensile strength, stability studies, in-vitro release, and mass balance studies. Further films were cross-linked in order to extend the drug release. Average weight and thickness among the different films was uniform. Tensile strength was maximum for plain films and minimum for films containing the highest percentage of the drug or cross-linked films. The stability studies did not show any significant changes. Static dissolution studies showed a burst release initially followed by a progressive fall in the release of the drug, and also showed extended release when cross-linking was attempted. The in-vitro release kinetics of tetracycline followed the zero order pattern. The fact that the mass balance studies done after in-vitro dissolution did not deviate by more than 3% from the experimental drug content, confirms that the drug is in free form rather than bound to the polymer.

The objective of the present work is to envisage and develop hollow calcium pectinate beads for floating pulsatile release of aceclofenac intended for chronopharmacotherapy. Floating pulsatile concept was applied to increase the gastric residence of the dosage form having lag phase followed by a burst release. The method used for the development of the beads was a simple process of acid-base reaction during ionotropic cross linking. The floating beads obtained were porous, hollow with a bulk density <1 and had an F _t50 of 14-24h. The floating beads showed a two-phase release pattern with initial lag phase during floating in an acidic medium followed by rapid pulse in phosphate buffer. The approach indicates the use of hollow calcium pectinate microparticles as a promising floating pulsatile drug delivery system for site- and time-specific release of drug acting as per chronotherapy of disease.

For the effective treatment of periodontitis, ciprofloxacin hydrochloride (HCl) medicated dental gels are prepared with different hydrophilic polymers (MC, HPMC, HPC, and HEC) in different concentrations of propylene glycol. The formulations are subjected to various physicochemical studies like pH, spreadability, extrudability, viscosity, drug content, in vitro drug release, and rheological and stability studies. During the rheological studies plots of shear rate versus viscosity showed that all the gels were non-Newtonian and exhibited pseudoplastic behavior. in vitro drug release studies were carried out in the diffusion cell using a pH 7.2 phosphate buffer as a receptor medium. Formulations exhibited an extended release of the drug for over a period of 6 hours and the release depended on the type of polymer and concentrations of propylene glycol used. Stability studies showed no significant variations ( P > 0.05) in pH, spreadability, viscosity, extrudability, and drug content. An in vitro release study concluded that hydrocolloid based ciprofloxacin hydrochloride medicated dental gels appear to be probably extend the release of ciprofloxacin hydrochloride. Optimal formulations were selected for in vivo or clinical studies. The clinical evaluation of ciprofloxacin hydrochloride gels was carried out to determine the efficacy in the treatment of periodontitis. Six groups, each containing five patients, were used in the study. All the patients were evaluated for plaque index (PI) and gingival index (GI), probing depth (PD), and bleeding on probing (BOP). In all these studies, two groups were treated with formulations alone and another two groups were treated with formulations along with scaling and root planning. One group was treated with scaling and root planning only, whereas, the last group was treated as control (No treatment). All the groups showed a similar baseline PI. However, the PI values decreased remarkably in the groups treated with formulation along with scaling and root planning when compared to the other groups. Similarly, the results of GI, BOP, and PD also showed a significant reduction ( P < 0.05) in the groups treated with formulation along with scaling and root planning compared to other groups. The above studies revealed that the adjunctive use of ciprofloxacin hydrochloride gels along with scaling and root planning results in significant benefits, in the treatment of periodontitis.

Theophylline-loaded agar microspheres were prepared and the effect of hydrocolloid on the physicochemical properties of the microspheres was investigated. Microspheres were prepared by the w/o emulsion solvent evaporation technique. Microspheres were spherical and free flowing, with particle size in the range of 105-123 µm. It was found that as the concentrations of the polymer and the hydrocolloid increased, the percentage yield, percentage encapsulation and percentage drug content also increased. An in vitro dissolution study was conducted according to the USP method (USP XXII) using apparatus I for 8 h. The dissolution profile of the developed formulation was compared with the marketed product (Theo SR). The similar results of prepared formulation (t ₅₀ = 211.78) and marketed product (t ₅₀ = 209.29) suggest sustained release of the drug.

High molecular weight hydroxypropyl methylcellulose (HPMC) and biodegradable pectin were used for coating the pellets containing curcumin, to be released in the colon. The prepared pellets were free flowing. in vitro release of curcumin remained intact up to pH 3.0, disintegrated at pH 7.2, and released up to 12 hours. The ideal batch (1:3) showed minimum release at pH 1.2 and maximum release at pH 6.8, and an increased amount of curcumin in the blood stream(1.287 µg/ml) was achieved when compared with pure curcumin (0.5 µg/ml). The drug release was retarded by the high concentration and greater thickness of the coating of HPMC on the pellets. Release kinetics of the preparation shows a non-Fickian or anamolous diffusion or matrix erosion.

The aim of the present study was to formulate an anti-epileptic drug-loaded microemulsion for nose-to-brain delivery. The oil system evaluated for the preparation of a stable microemulsion was iso-propyl myristate. A non-ionic surfactant like Tween 80 was used with polyethylene glycol 400 as a co-surfactant. A pseudoternary phase diagram for various proportions of S _mix :oil was constructed by the water titration method. The effect of changing concentration of alcohol as a co-surfactant was also studied. The t-phase diagram shows that the water consumption capacity of the system was increased as the surfactant concentration was increased. It was also found that as the concentration of the alcohol was increased, the viscosity of the microemulsion decreased. After the identification of the microemulsion region, the composition of the microemulsion was fixed at oil 9-10%, S _mix 35-40% and water 45-50%. The formulated microemulsion was evaluated for various parameters like pH, conductivity, zeta potential, viscosity and in vitro drug diffusion studies. All the evaluation parameters showed satisfactory results. Using this microemulsion, the solubility of valproic acid was increased from 1.29 to 36 mg/ml. Diffusion studies have shown a lag period of 45 min. Thirteen percent drug diffusion was achieved in 3 h. The prepared microemulsion was stable at 40°C and 75% relative humidity.

Non-steroidal anti-inflammatory drugs (NSAIDs) contain a wide range of effective drugs that use in treatment of inflammatory diseases. Chemical agents of non-steroidal anti-inflammatory drugs including diclofenac sodium, indomethacin and mefenamic acid, were screened for antibacterial activity by using two methods: Disc diffusion assay and spectrophotometer technique. From the results of disc diffusion method, Staphylococcus aureus exhibited susceptibility to diclofenac sodium and mefenamic acid. While, spectrophotometer method showed that Paracoocus yeei was susceptible to all tested compounds. Diclofenac sodium had loweress MIC (2.5mg/ml) to inhibit all of seven isolated strains. The application of spectrophotometer technique in this study considers more suitable method than those of disc diffusion test to reveal antibacterial activities of tested agents, especially with indomethacin.

The inherent property of gellan gum to gel and form circular beads through a process of ionotropic gelation in the presence of cations was utilized in the formulation of hydrochlorothiazide (HCTZ). The prepared beads exhibited good drug entrapment efficiency, content uniformity, and sustained release potential. The gelatin-HCTZ beads could be utilized in the delivery of HCTZ, by which reduced frequency of the drug administration could be achieved.

Oral sustained release gastroretentive dosage forms offer many advantages for drugs having absorption from the upper gastrointestinal tract and improve the bioavailability of medications that are characterized by the narrow absorption window. A new gastroretentive sustained release delivery system using the novel effervescent system was developed with floating, swellable, and bioadhesive properties. Various release retarding polymers like psyllium husk, HPMC K15M, and a swelling agent crosspovidone in different combinations were tried and optimized to get the release profile for 12hours. The formulations were evaluated for physicochemical characteristics, in vitro drug release profile, swelling characteristics, floating capacity, and in vitro bioadhesive property. i0 n vitro drug release followed the Higuchi kinetics and the release mechanism was found to be of a non-Fickian type. The swelling properties were increased with increasing crosspovidone concentration and contributed to the drug release from the tablet matrix. In this study, an attempt has been made to explore novel effervescent agents such as citroglycine and disodium glycine carbonate for achieving the desired floating time.