ABSTRACT
In the present study controlled release effervescent buccal discs of buspirone hydrochloride (BS) were designed using HPMC as rate controlling and bioadhesive polymer by direct compression method. Sodium bicarbonate and citric acid were used in varying amounts as effervescence forming agents. Carbon dioxide evolved due to reaction of sodium bicarbonate and citric acid was explored for its potential as buccal permeation enhancer. The designed buccal discs were evaluated for physical characteristics and in vitro drug release studies. Bioadhesive behavior of designed buccal discs was assessed using texture analyzer. In vivo animal studies were performed in rabbits to study bioavailability of BS in the designed buccal discs and to establish permeation enhancement ability of carbon dioxide. It was observed that effervescent buccal discs have faster drug release compared to non-effervescent buccal discs in vitro and effervescent buccal discs demonstrated significant increase in bioavailability of drug when compared to non-effervescent formulation. Hence, effervescent buccal discs can be used as an alternative to improve the drug permeation resulting in better bioavailability. However, the amount of acid and base used for generation of carbon dioxide should be selected with care as this may damage the integrity of bioadhesive dosage form.
Subject(s)
Buspirone/administration & dosage , Buspirone/pharmacokinetics , Dopamine D2 Receptor Antagonists/administration & dosage , Dopamine D2 Receptor Antagonists/pharmacokinetics , Drug Carriers , Hypromellose Derivatives/chemistry , Serotonin Receptor Agonists/administration & dosage , Serotonin Receptor Agonists/pharmacokinetics , Adhesiveness , Administration, Buccal , Animals , Biological Availability , Buspirone/chemistry , Carbon Dioxide/chemistry , Citric Acid/chemistry , Delayed-Action Preparations , Dopamine D2 Receptor Antagonists/chemistry , Dosage Forms , Drug Compounding , Gases , Male , Mouth Mucosa/metabolism , Oral Mucosal Absorption , Permeability , Rabbits , Serotonin Receptor Agonists/chemistry , Sodium Bicarbonate/chemistry , Solubility , Technology, Pharmaceutical/methodsABSTRACT
Delivery of orally compromised therapeutic drug molecules to the systemic circulation via buccal route has gained a significant interest in recent past. Bioadhesive polymers play a major role in designing such buccal dosage forms, as they help in adhesion of designed delivery system to mucosal membrane and also prolong release of drug from delivery system. In the present study, HPMC (release retarding polymer) and mannitol (diluent and pore former) were used to prepare bioadhesive and controlled release buccal discs of buspirone hydrochloride (BS) by direct compression method. Compatibility of BS with various excipients used during the study was assessed using DSC and FTIR techniques. Effect of mannitol and HPMC on drug release and bioadhesive strength was studied using a 3(2) factorial design. The drug release rate from delivery system decreased with increasing levels of HPMC in formulations. However, bioadhesive strength of formulations increased with increasing proportion of HPMC in buccal discs. Increased levels of mannitol resulted in faster rate of drug release and rapid in vitro uptake of water due to the formation of channels in the matrix. Pharmacokinetic studies of designed bioadhesive buccal discs in rabbits demonstrated a 10-fold increase in bioavailability in comparison with oral bioavailability of buspirone reported.
ABSTRACT
In the present study, for the first time, experimental pKa value of felodipine is reported. Dissociation constant, pKa, is one of the very important physicochemical properties of drugs. It is of paramount significance from the perspective of pharmaceutical analysis and dosage form design. The method used for the pKa determination of felodipine was essentially a UV-Visible spectrophotometric method. The spectrophotometric method for the pKa determination was opted by acknowledging the established fact that spectrophotometric determination of pKa produces most precise values. The pKa of felodipine was found to be 5.07. Furthermore, the ruggedness of the determined value is also validated in this study in order to produce exact pKa of the felodipine.
Subject(s)
Felodipine/chemistry , Absorption , Buffers , Hydrogen-Ion Concentration , Reproducibility of Results , Solutions , Spectrophotometry, UltravioletABSTRACT
Bioadhesive polymers in buccal drug delivery systems play an important role in delivery of therapeutic drug molecules for local and systemic action. Xanthan gum, a GRAS listed natural polymer was used to design buccal discs of buspirone hydrochloride by direct compression method. Effect of calcium sulfate on bioadhesive and drug release behavior of xanthan gum buccal discs was studied. Varying amount of calcium sulfate (0%, 5%, 10%, 20%, 30%, 40% and 50%, w/w) in combination with xanthan gum was used to prepare buccal bioadhesive discs. Increase in calcium sulfate concentration resulted in faster drug release and decreased the bioadhesive strength of the designed discs. Further, in rheological evaluation it was observed that viscosity of xanthan gum gel reduces with increasing concentration of calcium sulfate. Compatibility of drug with various excipients was assessed using DSC and FTIR techniques.
