Solid dispersions

Nimodipine, a poorly soluble drug, was considered to be fit for solid dispersions to improve its solubility and bioavailability. Our study intended to prepare Nimodipine solid dispersions by solvent evaporation method using various novel polymers. Solubility and dissolution studies indicate that Kolliwax RH 40 and SLS is the most suitable polymer. The solubility studies were corresponded with dissolution data and the formulation SD15 was found to be having highest drug release of about 98.96±5.15% in about 90 minutes. In-vitro release data from several formulations containing XRD and SEM studies indicate no crystallinity in the optimized formulation SD15. FTIR studies suggested good drug excipient compatibility between all components of prepared formulation. From in vivo bioavailability studies, Cmax of the optimized formulation SD15 was 4.34±0.08ng /ml, was significantly higher as compared to pure drug suspension, i.e., 2.78±0.35ng/ml. Tmax of optimized formulation was decreased significantly when compared with pure drug (1.00±0.05hr, 2.00±0.01hr), AUC0-? and AUC0-t for optimized solid dispersion formulation was significantly higher (p<0.05) as compared to pure drug suspension. The present study demonstrated that formulation of Nimodipine solid dispersion by solvent evaporation technique is a highly effective strategy for enhancing the bioavailability of poorly water soluble Nimodipine.

The major problem in formulation of oral films of cilnidipine is that it belongs to BCS Class II moiety. Pharmacologically Cilnidipine is a dihydropyridine (DHP) type of calcium channel antagonist. Unlike other calcium channel antagonists, Cilnidipine blocks the influx of Ca2+ ions into both vascular smooth muscle at the level of L-type Ca2+ channels and neuronal cells at the level of N-type Ca2+ channels. Cilnidipine was absorbed over 2 hours and its bioavailability is 64-90%. Hence there is a need to increase the solubility and oral bioavailability of cilnidipine by formulating it in to solid dispersions and incorporating the same in to the formulation of fast dissolving films which gives fast onset of action. Nine formulations (FC 1 - FC 9) of cilnidipine films were prepared and evaluated for their physical characteristics such as thickness, weight variation, folding endurance, drug content uniformity and gave satisfactory results. The compatibility of the drug in the formulation was confirmed by FTIR and DSC studies. The formulations were subjected to disintegration, in vitro drug release studies and formulation FC 6 was found to be best formulation which contain HPMC, PVP as film forming polymers along with cilnidipine solid dispersion with poly ethylene glycol at weight ratio of 1:4 showed excellent film forming characteristics such as disintegration time of 49.3 sec and percentage drug release 97.92 within 8 minutes.

Silymarin, a hepatoprotective agent has poor aqueous solubility and high permeability [class II drug]. Its absorption is dissolution rate limited. In order to improve the dissolution profile of silymarin solubility enhancement techniques were employed. Among the various techniques, solid dispersions were employed due to its feasibility. Polymers used were HPMC and PEG. Silymarin was formulated by kneading method and solvent evaporation method, where HPMC and PEG were used in different ratios of drug: polymer. Polymer characterization for the prepared solid dispersion was done using FT-IR, XRPD, SEM and DSC. In vitro dissolution studies were carried out in 0.1M HCl and phosphate buffer mixed (pH 6.8). From the in vitro studies, dissolution efficiency and drug release kinetics was also calculated. FT-IR studies revealed that there was no interaction between the drug and the polymers used. DSC, XRPD and SEM supported the existence of silymarin in amorphous state, in the prepared solid dispersions. Drug content analysis showed maximum drug release of 101.03 for solid dispersion prepared using drug: HPMC in the ratio of 1:3 [KM2] using polysorbate 80, employing kneading method. In vitro release of KM2 was found to be 98.87 ± 0.32 in 0.1 M HCl buffer.  Kneading method proved to be superior to solvent evaporation method. Compared to the pure drug silymarin, solid dispersions [KM2] gave a 2.2 fold increase in the dissolution profile.

Water soluble drugs if not formulated properly, may release the drug at a faster rate and produce a toxic concentration on administration. Captopril belongs to the class I of biopharmaceutical classification system (BCS) has short half life (~2hrs) shows dose dumping, burst and stability in acidic pH of stomach. In this study HPMC K15M and Compritol 888 ATO alone and in combination different proportions using physical mixture and solid dispersion method to prepare floating matrix tablet. The tablets were evaluated for appearance, weight variation, hardness, friability, floating lag time, duration and integrity of matrices, In-vitro and In vivo drug release kinetics. IR spectra, thermal behavior and X-ray diffraction pattern of selected solid dispersions were carried out indicating no degradative changes. The rate of release of Captopril from floating matrix tablets containing physical mixtures was found to be affected by the concentration of Compritol 888 ATO increase in the concentration decrease the release. Among the formulations containing solid dispersions of drug with Compritol888 ATO (SPC3c’’) give retardation of drug release (t90% >12) for extended time. All formulations indicated diffusion exponent (n) values in the range 0.4 to 0.6 suggesting Fickian diffusion. The values of ‘n’ increased with increase in concentration of lipid polymers suggesting a shift in the mechanism of drug release from Fickian to anomalous. All formulations show initial burst release which may due to high water solubility of Captopril. The X-Ray photographs indicated the residence of tablet in stomach for about 5hs.

  Solid dispersion is a widely accepted technique for enhancing the dissolution rate of poorly soluble BCS class II drugs. In the present study starch phosphate- a new modified starch, PVP and PEG 4000 were evaluated as a carriers in solid dispersions for enhancing the dissolution rate and efficiency of nimesulide, a BCS class II drug. Their individual and combined (interaction) effects in enhancing the dissolution rate and dissolution efficiency of nimesulide were evaluated in a 23- factorial study. Among the individual effects PEG 4000 gave highest enhancement in the dissolution rate of nimesulide (14.23 fold), followed by starch phosphate (11.34 fold). Addition of PVP and PEG 4000 to the solid dispersions in starch phosphate has further enhanced the dissolution rate upto 75.70 fold and dissolution efficiency upto 26.67 fold.   Key words: Solid dispersions, Nimesulide, Starch Phosphate, PVP, PEG 4000, Factorial Study.

  The objective of present study is to improve the dissolution rate of Acyclovir a poorly water soluble drug by solid dispersion technique using a water soluble carrier, PEG-6000, urea, mannitol. The solid dispersions are prepared by physical method, co-grinding method and solvent evaporation method. The prepared solid dispersions showed an enhancement in dissolution rate and solubility compared to plain drug. In vitro release profiles of all SDs were comparatively evaluated and also studied against pure acyclovir. Faster dissolution was exhibited by solid dispersion containing 1:4 ratio of drug: PEG-6000. The increase in dissolution rate of the drug may be due to increase in wettability, hydrophilic nature of the carrier and due to reduction in drug crystallinity. The prepared solid dispersion was subjected for % practical yield, drug content, infrared (IR) spectroscopic, differential scanning calorimetry (DSC). FT‐IR spectra revealed no chemical incompatibility between drug and PEG-6000.Drug– polymer interaction was investigated using differential scanning calorimetry (DSC) studies. Key words: Solid dispersions, carriers, solubility enhancement, poorly soluble drugs, bioavailability