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The purpose of this research was to develop; evaluate buccal mucoadhesive controlled release tablets of lercanidipine hydrochloride using polyethylene oxide; different viscosity grades of hydroxypropyl methylcellulose individually; in combination. Effect of polymer type, proportion; combination was studied on the drug release rate, release mechanism; mucoadhesive strength of the prepared formulations. Buccal mucoadhesive tablets were made by direct compression; were characterized for content uniformity, weight variation, friability, surface pH, thickness; mechanism of release. In order to estimate the relative enhancement in bioavailability one optimized formulation was evaluated in rabbits. Further, placebo tablets were also evaluated for acceptability in human subjects. Results indicated acceptable physical characteristics of designed tablets with good content uniformity; minimum weight variation. Drug release; mucoadhesive strength were found to depend upon polymer type, proportion; viscosity. The formulations prepared using poly ethylene oxide gave maximum mucoadhesion. The release mechanism of most formulations was found to be of anomalous non-Fickian type. In vivo studies of selected formulation in rabbits demonstrated significant enhancement in bioavailability of lercanidipine hydrochloride relative to orally administered drug. Moreover, in human acceptability studies of placebo formulations, the designed tablets adhered well to the buccal mucosa for more than 4 h without causing any discomfort. It may be concluded that the designed buccoadhesive controlled release tablets have the potential to overcome the disadvantage of poor; erratic oral bioavailability associated with the presently marketed formulations of lercanidipine hydrochloride.
Shrikant Charde1 Email:shrikanthcharde@bits-pilani.ac.in Madri Mudgal1 Lajwinder Kumar1 Ranendra Saha1
[1] Formulation Development; Pharmacokinetics Laboratory, Pharmacy Group, Birla Institute of Technology; Science, Pilani- 333031 Rajasthan, India
The objective of this investigation was to evaluate the potential of the microemulsions to improve the parenteral delivery of propofol. Pseudo-ternary phase diagrams were plotted to identify microemulsification region of propofol. The propofol microemulsions were evaluated for globule size, physical; chemical stability, osmolarity, in vitro hemolysis, pain caused by injection using rat paw-lick test; in vivo anesthetic activity. The microemulsions exhibited globule size less than 25 nm; demonstrated good physical; chemical stability. Propofol microemulsions were slightly hypertonic; resulted in less than 1% hemolysis after 2 h of storage with human blood at 37 °C. Rat paw-lick test indicated that propofol microemulsions were significantly less painful as compared to the marketed propofol formulation. The anesthetic activity of the microemulsions was similar to the marketed propofol formulation indicating that they do not compromise the pharmacological action of propofol. The stability studies indicated that the microemulsions were stable for 3 months when stored at 5±3 °C. Thus, microemulsions appeared to be an interesting alternative to the current propofol formulations.
Abhijit A. Date1 Mangal S. Nagarsenker1 Email:mangal_nag511@yahoo.co.in
[1] Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz [E.], Mumbai, 400098, India
2008, no20
The aim of this research was to formulate Marsupsin–phospholipid complex (M–P Complex) in attempt to increase the bioavailability of marsupsin; to characterize this new formulation along with its evaluation. Marsupsin–phospholipid complex was formulated by mechanical dispersion method. In this new formulation, complex formation was confirmed by carrying out transmission electron microscopy (TEM), IR, [1]H-NMR; RP-HPLC analysis. TEM showed M–P Complex diameter range of 0.05–0.5 μm. The entrapment efficiency of M–P Complex was found to be 44%. In vitro release study revealed its first order release profile. Mean blood serum concentration vs time curve of marsupsin was of first order after oral administration of M–P Complex in albino rabbits which clearly showed remarkably increased bioavailability of M–P Complex than standardized marsupsin. The average value of C max; T max of M–P Complex were found to be 3.02 mg/ml; 10.2 h, respectively. Hence the findings demonstrate that complexing marsupsin with phospholipids results in better oral bioavailability; improved biological response than free form of standardized marsupsin.
Mukesh S. Sikarwar1 Email:mukeshsikarwar@gmail.com Shalini Sharma2 Amit K. Jain1 S. D. Parial1
[1] Department of Pharmacognosy; Phytochemistry, B. R. Nahata College of Pharmacy, Mhow-Neemuch Road, Mandsaur, 458001, India ;[2] Department of Dravyaguna, D. G. M. Ayurvedic Medical College, Kalashpur Road, Gadag, Karnataka, India
The present studies were designed to develop a formulation of amphotericin B in a lipid-based preparation as a microemulsion; to compare its toxicity with the commercial formulation Fungizone. The final product developed is a lyophilized amphotericin B, oil; surfactant blend for reconstitution in water to yield a microemulsion containing 5 mg/ml of the drug. Pseudoternary phase diagrams were constructed to identify areas of existence of microemulsion composed of Peceol (glyceryl monooleate) as oil phase; Mys 40 (polyethylene glycol 40 stearate); Solutol HS 15 (polyethylene glycol 15 hydroxy stearate) as surfactants. Amphotericin B was co-evaporated with oil – surfactant mixture to produce a microemulsion pre-concentrate. The co-evaporate was diluted in water, filtered for sterilization; lyophilized to obtain the final product. The lyophilized as well as the reconstituted products were separately studied for stability; the latter was also characterized for various physicochemical aspects including droplet size of the dispersed phase, osmolarity; aggregation state of drug. The dispersion showed no evidence of precipitation of drug for 48 h,; resisted destabilization due to freeze–thaw cycles or centrifugation. The dispersed phase globules measured a mean size of 84 nm; uv–spectrophotometric studies indicated the presence of self-aggregated amphotericin B. The present formulation showed a 92% decrease in haemolysis of human RBC in vitro when compared with the commercially available Fungizone. The LD50 in mice was estimated to be 3.4 mg/kg. The results indicate that the formulation holds promise for development as a safer; efficacious alternative for amphotericin B therapy.
Pradnya S. Darole1 Darshana D. Hegde1 Hema A. Nair1 Email:hemastudent@gmail.com
[1] Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz ;[E.], Mumbai, 400098, Maharashtra, India
The purpose of the present study was to investigate the potential use of two PEGylated derivatives of rosin (PD) as sustained release film forming materials. The derivatives differed chemically by their acid numbers—PD-1 with 120.93; PD-2 with 88.19. The derivative films were characterized for surface morphology, water uptake-weight loss, angle of contact, water vapor transmission rate, mechanical properties; permeability study. Dissolution of diclofenac sodium (DS); propranolol hydrochloride (PHL) as model drugs was studied from coated pellets. The films of derivatives with; without plasticizers were smooth; continuous. PD-2 films developed greater numbers of pores when in contact with phosphate buffer pH 6.8. The low weight loss, low angles of contact; high water vapor transmission rate of PD-2 films were related to presence of higher concentration of PEG esters. Higher tensile strength; percent elongation of PD-2 films was due to greater degree of internal plasticization of the derivative. The permeability of films to model drugs propranolol hydrochloride; diclofenac sodium was inversely proportional to the film thickness; dibutyl phthalate concentration in them; the permeability being greatest in PD-2 films containing 10% PEG 200. Dissolution rate of propranolol hydrochloride was higher from the coated pellets. The dissolution data followed zero order, Baker–Lonsdale equation; Hixon–Crowell equation of release kinetics with high correlation coefficients. The mechanism of drug release from these coated systems however followed class II transport (n>1.0). The derivatives investigated could successfully retard release of the model drugs; offers an alternative to the conventionally used polymers.
V. S. Nde1Email:nandevs@rediffmail.com U. V. Barabde1 D. M. Morkhade1 S. B. Joshi1 A. T. Patil1
[1] Department of Pharmaceutical Sciences, Nagpur University Campus, Nagpur, 440 033, Maharashtra, India ;[2] Present address: Wockhardt Research Center, D-4 MIDC Area, Chikalthana, Aurangabad, 431 210, Maharashtra, India
2008,no15
The purpose of this study was to develop a dosage form that was easy to administer; provides rapid release of the drug roxithromycin, using modified polysaccharides as rapidly disintegrating excipients. Modified polysaccharides co grinded treated agar (C-TAG); co grinded treated guar gum (C-TGG) were prepared by subjecting pure polysaccharides namely agar; guar gum respectively to sequential processes of wetting, drying; co grinding with mannitol (1:1). The modified polysaccharides were characterized by Scanning Electron Microscopy; Diffuse Reflectance Spectroscopy; evaluated for particle size distribution, derived properties, swelling index; biodegradability. Optimization studies based on 2[2] factorial designs, with friability; disintegration time as response parameters were used to formulate orodispersible tablets of roxithromycin; evaluated for wetting time, water absorption ratio; in vitro drug release at salivary pH 6.4; physiological pH 7.4. Results indicated that lower levels of modified polysaccharides namely C-TAG in F3; C-TGG in F7; higher levels of microcrystalline cellulose, exhibited least disintegration times without friability concerns. In vitro release of optimized formulations F3; F7, both at salivary pH; physiological pH was found to be more than 90% within 30 min as compared to 27.82% at the same time point of conventional formulation. Stability studies carried out as per ICH Q1A guidelines suggested the formulations to be stable for a period of 6 months. Thus the approach of using modified polysaccharides as fast disintegrating excipient can be used to formulate a stable orodispersible formulation.
Vijay Sharma1 Anil K. Philip1 Kamla Pathak1 Email:kamla_rap@yahoo.co.in
[1] Department of Pharmaceutics, Rajiv Academy For Pharmacy, NH#2, Delhi–Mathura bypass, P. O. Chattikkara, Mathura, 281001, Uttar Pradesh, India
In the present study, the aim was to optimize an orodispersible formulation of indomethacin using a combined approach of subliming agent; superdisintegrant. The tablets were made by non-aqueous wet granulation technique with superdisintegrant incorporated both intragranularly; extragranularly. A 2[3] factorial design was used to investigate the effects amount of subliming agents namely camphor; ammonium bicarbonate; taste masking; soothening hydrophilic agent mannitol as independent variables; disintegration time; crushing strength as dependent responses. The volatilization time of eight hours at 50°C was optimized by conducting solid-state kinetic studies of optimized formulations. Optimized orodispersible tablets were evaluated for wetting time, water absorption ratio, porosity; in vitro; in vivo disintegration tests. Results show that higher levels of camphor; mannitol; a lower level of ammonium bicarbonate is desirable for orodispersion. Scanning electron microscopy (SEM) revealed the porous surface morphology; kinetic digital images substantiated the orodispersible property. Differential Scanning Calorimetry (DSC) studies exhibited physiochemical compatibility between indomethacin; various excipients used in the tablet formulation. Stability studies carried out as per ICH Q1 A guidelines suggested the stable formulations for the tested time period of 6 months. The systematic approach of using subliming; disintegrating agents helped in achieving a stable, optimized orodispersible formulation, which could be industrially viable.
Jashanjit Singh1 Anil K. Philip1 Kamla Pathak1 Email:kamla_rap@yahoo.co.in
[1] Department of Pharmaceutics, Rajiv Academy For Pharmacy, NH#2, Delhi- Mathura bypass, P.O. Chattikkara, Mathura, 281001, Uttar Pradesh, India
number 8
This investigation was undertaken to evaluate practical feasibility of site specific pulmonary delivery of liposomal encapsulated Dapsone (DS) dry powder inhaler for prolonged drug retention in lungs as an effective alternative in prevention of Pneumocystis carinii pneumonia (PCP) associated with immunocompromised patients. DS encapsulated liposomes were prepared by thin film evaporation technique; resultant liposomal dispersion was passed through high pressure homogenizer. DS nano-liposomes (NLs) were separated by ultra centrifugation; characterized. NLs were dispersed in phosphate buffer saline (PBS) pH 7.4 containing different carriers like lactose, sucrose,; hydrolyzed gelatin,; 15% l-leucine as antiadherent. The resultant dispersion was spray dried; spray dried formulation were characterized to ascertain its performance. In vitro pulmonary deposition was assessed using Andersen Cascade Impactor as per USP. NLs were found to have average size of 137±15 nm, 95.17±3.43% drug entrapment,; zeta potential of 0.8314±0.0827 mV. Hydrolyzed gelatin based formulation was found to have low density, good flowability, particle size of 7.9±1.1 μm, maximum fine particle fraction (FPF) of 75.6±1.6%, mean mass aerodynamic diameter (MMAD) 2.2±0.1 μm,; geometric standard deviation (GSD) 2.3±0.1. Developed formulations were found to have in vitro prolonged drug release up to 16 h,; obeys Higuchi’s Controlled Release model. The investigation provides a practical approach for direct delivery of DS encapsulated in NLs for site specific controlled; prolonged release behavior at the site of action; hence, may play a promising role in prevention of PCP.
Mahavir Chougule1 Bijay Padhi1 Ambikan an Misra1 Email:misraan@hotmail.com
[1] TIFAC-CORE in NDDS, Pharmacy Department, Faculty of Technology; Engineering, The Maharaja Sayajirao University of Baroda, Kalabhavan, Vadodara, 390 001, Gujarat, India
The objective of present investigation was to formulate self-microemulsifying drug delivery systems (SMEDDS) of tacrolimus (FK 506), a poorly water soluble immunosuppressant that exhibits low; erratic bioavailability. Solubility of FK 506 in various oils, surfactants cosurfactants; buffers was determined. Phase diagrams were constructed at different ratios of surfactant/cosurfactant (K m ) to determine microemulsion existence region. The effect of oil content, pH of aqueous phase, dilution,; incorporation of drug on mean globule size of resulting microemulsions was studied. The optimized SMEDDS formulation was evaluated for in vitro dissolution profile in comparison to pure drug; marketed formulation (Pangraf capsules). The in vivo immunosuppressant activity of FK 506 SMEDDS was evaluated in comparison to Pangraf capsules. Area of o/w microemulsion region in phase diagram was increased with increase in K m . The SMEDDS yielded microemulsion with globule size less than 25 nm which was not affected by the pH of dilution medium. The SMEDDS was robust to dilution; did not show any phase separation; drug precipitation even after 24 h. Optimized SMEDDS exhibited superior in vitro dissolution profile as compared to pure drug; Pangraf capsules. Furthermore, FK 506 SMEDDS exhibited significantly higher immunosuppressant activity in mice as compared to Pangraf capsules.
Vivek Borhade1 Hema Nair1 Darshana Hegde1 Email:ddhegde2003@yahoo.co.in
[1] Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz ;[E.], Mumbai, 400098, Maharashtra, India
The purpose of this research was to explore theapplication of ionic interactions between naproxen sodium (NS); chitosan (CH) in complexes (NSC) prepared by tray drying (TD); spray drying (SD) methods. Drug–polymer ratio (1:1) in the NSC was optimized on the basis of dialysis studies. The particulate systems of NSC were prepared by tray drying (TD); spray drying (SD) methods. Release retarding polymers were added to the NSC; to the physical mixtures containing NS–CH; their effects on water uptake, matrix erosion; drug release at different pH were compared. Spray dried complexes (SDC) were spherical, free flowing, light; fine amorphous particles in contrast to the crystalline, hard, tenacious, irregularly shaped, denser tray dried complexes (TDC) with poor flowability. Differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD); Fourier transform infrared (FTIR) patterns confirm the conversion of crystalline to high energy amorphous phase suitable for ionic interactions in NSC. Presence of release retarding polymers, kappa carrageenan; hydroxypropylmethylcellulose (HPMC) in the NSC compacts retarded the drug release; improved the matrix integrity. Carrageenan matrices exhibited more retardation than HPMC tablets. FTIR patterns, erosion, swelling; drug release from matrices support ionic interactions between NS; CH in NSC. The reasons for retarded drug release from the chitosan matrices at acidic pH include poor solubility of drug at acidic pH, formation of a rate limiting polymer gel barrier along the periphery of matrices; the ionic interactions between oppositely charged moieties.
Kiran S. Bhise1 Ravindra S. Dhumal1 Anant R. Paradkar1 Email:arparadkar@rediffmail.com Shivajirao S Kadam1
[1] Department of Pharmaceutics, Bharati Vidyapeeth University, Poona College of Pharmacy, Erandawane, Paud Road, Pune, 411038, Maharashtra, India